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Nonaka D, Kishida M, Hirata Y, Mori A, Kondo A, Mori Y, Noda S, Tanaka T. Metabolic Engineering for Resveratrol Production Based on Modularization of Metabolic Pathways in Escherichia coli. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2025; 73:11878-11888. [PMID: 40305421 DOI: 10.1021/acs.jafc.5c00804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/02/2025]
Abstract
Separating metabolic pathways for microbial chemical production is a promising approach for allocating resources based on target compounds. We modularized an artificial resveratrol biosynthetic pathway in Escherichia coli to supply p-coumaric acid and malonyl-CoA as precursors independently via the coutilization of glucose and xylose. The optimization of resveratrol synthetic gene expression, sugar concentration, and Corynebacterium glutamicum pyc overexpression improved the resveratrol titer in the engineered strain. Furthermore, introducing acetate into the malonyl-CoA supply module as a third carbon source resulted in an increased resveratrol titer. The cultivation of a strain overexpressing pyc and resveratrol synthetic genes in a 1-L bioreactor produced 273.5 mg/L resveratrol. The modularization of metabolic pathways to supply p-coumaric acid and malonyl-CoA from independent sources, such as sugars and acetate, enabled resveratrol production. Overall, this study contributes to the high production of chemicals whose biosynthetic pathways require multiple precursors such as polyketide.
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Affiliation(s)
- Daisuke Nonaka
- Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8501, Japan
| | - Mayumi Kishida
- Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8501, Japan
| | - Yuuki Hirata
- Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8501, Japan
| | - Ayana Mori
- Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8501, Japan
| | - Akihiko Kondo
- Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8501, Japan
| | - Yutaro Mori
- Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8501, Japan
| | - Shuhei Noda
- Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8501, Japan
- PRESTO, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan
| | - Tsutomu Tanaka
- Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8501, Japan
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Li W, Weng Y, Ma H, Hu X, Ren L. Improving ergothioneine content in Pleurotus citrinopileatus through two-stage oxidative stimulus strategy. BIORESOURCE TECHNOLOGY 2025; 431:132630. [PMID: 40348064 DOI: 10.1016/j.biortech.2025.132630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2025] [Revised: 04/28/2025] [Accepted: 05/05/2025] [Indexed: 05/14/2025]
Abstract
Mushroom is an important agricultural crop, rich in various nutrients and bioactive compounds. Ergothioneine (EGT), a naturally occurring antioxidant, is found in mushrooms that offers significant health benefits. This study developed a two-stage oxidative stimulus strategy to enhance the EGT content. After screening 11 species of macrofungi, P. citrinopileatus 303 was selected. With the cultivation conditions optimized, EGT titer reached 533.93 mg/L. To further boost EGT synthesis, oxidative stress was introduced by hydrogen peroxide (H2O2). An optimized strategy combining oxidative stress with clearance was then implemented. Finally, a two-stage oxidative stimulus approach was employed, where the cells were first exposed to H2O2, followed by oxidative clearance using vitamin C in the second stage. This strategy increased the EGT titer to 641.76 mg/L, 5.83 times that of the initial group, with the fermentation time reduced to 5 days. It offered valuable insights for the industrial-scale biosynthesis of this potent antioxidant.
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Affiliation(s)
- Weiyi Li
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing 211816, People's Republic of China
| | - Yuwan Weng
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing 211816, People's Republic of China
| | - Huiguo Ma
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing 211816, People's Republic of China
| | - Xuechao Hu
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing 211816, People's Republic of China; Jiangsu JanStar Biotechnology Co., Ltd., No. 6, Dongsheng West Road, Jiangsu, People's Republic of China.
| | - Lujing Ren
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing 211816, People's Republic of China.
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3
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Costa CE, Romaní A, Domingues L. Overview of resveratrol properties, applications, and advances in microbial precision fermentation. Crit Rev Biotechnol 2024:1-17. [PMID: 39582165 DOI: 10.1080/07388551.2024.2424362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 01/03/2024] [Accepted: 07/13/2024] [Indexed: 11/26/2024]
Abstract
Resveratrol is an antioxidant abundant in plants like grapes and peanuts and has garnered significant attention for its potential therapeutic applications. This review explores its chemical attributes, stability, and solubility, influencing its diverse applications and bioavailability. Resveratrol's multifaceted therapeutic roles encompass: antioxidant, cardioprotective, anti-inflammatory, neuroprotective, anti-aging, and anticancer properties. While traditionally studied in preclinical settings, a surge in clinical trials underscores resveratrol's promise for human health. Over 250 recent clinical trials investigate its effects alone and in combination with other compounds. Commercially utilized in food, cosmetics, supplements, and pharmaceuticals, the resveratrol market is expanding, driven by microbial fermentation. Microbes offer advantages over plant extraction and chemical synthesis, providing cost-effective, pure, and sustainable production. Microbial biosynthesis can be attained from carbon sources, such as glucose or xylose, among others, which can be obtained from renewable resources or agro-industrial wastes. While Saccharomyces cerevisiae has been the most used host, non-conventional yeasts like Yarrowia lipolytica and bacteria like Escherichia coli have also demonstrated potential. Genetic modifications such as increasing acetyl-CoA/malonyl-CoA pools, boosting the shikimate pathway, or multi-copy expression of pathway genes, allied to the optimization of fermentation strategies have been promising in increasing titers. Microbial biosynthesis of resveratrol aligns with the shift toward sustainable and renewable bio-based compounds, exemplifying a circular bioeconomy. Concluding, microbial fermentation presents a promising avenue for efficient resveratrol production, driven by genetic engineering, pathway optimization, and fermentation strategies. These advances hold the key to unlocking the potential of resveratrol for diverse therapeutic applications, contributing to a greener and sustainable future.
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Affiliation(s)
- Carlos E Costa
- CEB - Centre of Biological Engineering, University of Minho, Braga, Portugal
- LABBELS - Associate Laboratory, Braga/Guimarães, Portugal
| | - Aloia Romaní
- Department of Chemical Engineering, Faculty of Science, University of Vigo (Campus Ourense), Ourense, Spain
| | - Lucília Domingues
- CEB - Centre of Biological Engineering, University of Minho, Braga, Portugal
- LABBELS - Associate Laboratory, Braga/Guimarães, Portugal
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An H, Li G, Yang Z, Xiong M, Wang N, Cao X, Yu A. Denovo Production of Resveratrol by Engineered Rice Wine Strain Saccharomyces cerevisiae HJ08 and Its Application in Rice Wine Brewing. J Fungi (Basel) 2024; 10:513. [PMID: 39194839 DOI: 10.3390/jof10080513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 07/17/2024] [Accepted: 07/22/2024] [Indexed: 08/29/2024] Open
Abstract
Resveratrol is a plant-derived polyphenolic compound with numerous biological activities and health-promoting properties. Rice wine is a popular traditional alcoholic beverage made from fermented rice grains, and widely consumed in Asia. To develop resveratrol-enriched rice wine, a heterologous resveratrol biosynthesis pathway was established by integrating the 4-coumaroyl-CoA ligase (Pc4CL) and the stilbene synthase (VvSTS) from Petroselinum crispum and Vitis vinifera at the δ locus sites of industrial rice wine strains Saccharomyces cerevisiae HJ. The resulting S. cerevisiae HJ01 produced a level of 0.6 ± 0.01 mg/L resveratrol. Next, the resveratrol production was increased 16.25-fold through employing the fused protein Pc4CL::VvSTS with a rigidly linked peptide (TPTP, EAAAK). Then, the strains were further modified by removing feedback inhibition of tyrosine through point mutation of ARO4 and ARO7, which integrated at the rDNA region of strain HJ03, and generated strain HJ06, HJ07, and HJ08. Subsequently, the highest resveratrol titer (34.22 ± 3.62 mg/L) was obtained by optimizing fermentation time and precursor addition amount. Finally, resveratrol content of rice wine fermented with strain HJ08 was 2.04 ± 0.08 mg/L and 1.45 ± 0.06 mg/L with or without the addition of 400 mg/L tyrosine after 7 days fermentation.
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Affiliation(s)
- Huihui An
- School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China
| | - Guangpeng Li
- School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China
| | - Zhihan Yang
- School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China
| | - Meng Xiong
- School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China
| | - Na Wang
- School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China
| | - Xitao Cao
- School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China
| | - Aiqun Yu
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, No. 29 the 13th Street TEDA, Tianjin 300457, China
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Jang Y, Lee YJ, Gong G, Lee SM, Um Y, Kim KH, Ko JK. Carbon dioxide valorization into resveratrol via lithoautotrophic fermentation using engineered Cupriavidus necator H16. Microb Cell Fact 2024; 23:122. [PMID: 38678199 PMCID: PMC11055273 DOI: 10.1186/s12934-024-02398-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 04/19/2024] [Indexed: 04/29/2024] Open
Abstract
BACKGROUND Industrial biomanufacturing of value-added products using CO2 as a carbon source is considered more sustainable, cost-effective and resource-efficient than using common carbohydrate feedstocks. Cupriavidus necator H16 is a representative H2-oxidizing lithoautotrophic bacterium that can be utilized to valorize CO2 into valuable chemicals and has recently gained much attention as a promising platform host for versatile C1-based biomanufacturing. Since this microbial platform is genetically tractable and has a high-flux carbon storage pathway, it has been engineered to produce a variety of valuable compounds from renewable carbon sources. In this study, the bacterium was engineered to produce resveratrol autotrophically using an artificial phenylpropanoid pathway. RESULTS The heterologous genes involved in the resveratrol biosynthetic pathway-tyrosine ammonia lyase (TAL), 4-coumaroyl CoA ligase (4CL), and stilbene synthase (STS) -were implemented in C. necator H16. The overexpression of acetyl-CoA carboxylase (ACC), disruption of the PHB synthetic pathway, and an increase in the copy number of STS genes enhanced resveratrol production. In particular, the increased copies of VvSTS derived from Vitis vinifera resulted a 2-fold improvement in resveratrol synthesis from fructose. The final engineered CR-5 strain produced 1.9 mg/L of resveratrol from CO2 and tyrosine via lithoautotrophic fermentation. CONCLUSIONS To the best of our knowledge, this study is the first to describe the valorization of CO2 into polyphenolic compounds by engineering a phenylpropanoid pathway using the lithoautotrophic bacterium C. necator H16, demonstrating the potential of this strain a platform for sustainable chemical production.
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Affiliation(s)
- Yongjae Jang
- Clean Energy Research Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
| | - Yeon Ji Lee
- Clean Energy Research Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
| | - Gyeongtaek Gong
- Clean Energy Research Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
- Division of Energy and Environment Technology, KIST School, University of Science and Technology, Seoul, 02792, Republic of Korea
| | - Sun-Mi Lee
- Clean Energy Research Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
- Division of Energy and Environment Technology, KIST School, University of Science and Technology, Seoul, 02792, Republic of Korea
| | - Youngsoon Um
- Clean Energy Research Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
- Division of Energy and Environment Technology, KIST School, University of Science and Technology, Seoul, 02792, Republic of Korea
| | - Kyoung Heon Kim
- Department of Biotechnology, Korea University, Seoul, 02841, Republic of Korea
| | - Ja Kyong Ko
- Clean Energy Research Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.
- Division of Energy and Environment Technology, KIST School, University of Science and Technology, Seoul, 02792, Republic of Korea.
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6
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Kulasekaran NT, Thilakam ML, Gopal D, Lee JK, Marimuthu J. Denovo production of resveratrol by engineered Saccharomyces cerevisiae W303-1a using pretreated Gracilaria corticata extracts. Biotechnol Lett 2024; 46:19-28. [PMID: 37987932 DOI: 10.1007/s10529-023-03441-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Revised: 09/05/2023] [Accepted: 10/01/2023] [Indexed: 11/22/2023]
Abstract
OBJECTIVE Assembly and construction of resveratrol production pathway in Saccharomyces cerevisiae for denovo production of resveratrol using seaweed extract as fermentation medium. RESULTS Genes involved in the production of resveratrol from tyrosine pathway, tyrosine ammonia lyase (FTAL) gene from Flavobacterium johnsoniae (FjTAL), the 4-coumarate:CoA ligase gene from Arabidopsis thaliana (4CL1) and the stilbene synthase gene from Vitis vinifera (VvSTS) were introduced into low copy, high copy and integrative vector and transformed into S. cerevisiae W303-1a. The resulting strains W303-1a/pARS-res5, W303-1a/2µ-res1 and W303-1a/IntUra-res9 produced a level of 2.39 ± 0.01, 3.33 ± 0.03 and 8.34 ± 0.03 mg resveratrol l-1 respectively. CRISPR mediated integration at the δ locus resulted in 17.13 ± 1.1 mg resveratrol l-1. Gracilaria corticata extract was tested as a substrate for the growth of transformant to produce resveratrol. The strain produced a comparable level, 13.6 ± 0.54 mg resveratrol l-1 when grown in seaweed extract medium. CONCLUSIONS The strain W303-1a/IntδC-res1 utilized Gracillaria hydrolysate and produced 13.6 ± 0.54 mg resveratrol l-1 and further investigations are being carried out focusing on pathway engineering and optimization of process parameters to enhance resveratrol yield.
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Affiliation(s)
| | - Mary Leema Thilakam
- Marine Biotechnology Division, National Institute of Ocean Technology, Chennai, 600100, India
| | - Dharani Gopal
- Marine Biotechnology Division, National Institute of Ocean Technology, Chennai, 600100, India
| | - Jung-Kul Lee
- Department of Chemical Engineering, Konkuk University, Seoul, 143 701, Korea
| | - Jeya Marimuthu
- Marine Biotechnology Division, National Institute of Ocean Technology, Chennai, 600100, India.
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Tramontina R, Ciancaglini I, Roman EKB, Chacón MG, Corrêa TLR, Dixon N, Bugg TDH, Squina FM. Sustainable biosynthetic pathways to value-added bioproducts from hydroxycinnamic acids. Appl Microbiol Biotechnol 2023:10.1007/s00253-023-12571-8. [PMID: 37212882 DOI: 10.1007/s00253-023-12571-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 05/01/2023] [Accepted: 05/05/2023] [Indexed: 05/23/2023]
Abstract
The biorefinery concept, in which biomass is utilized for the production of fuels and chemicals, emerges as an eco-friendly, cost-effective, and renewable alternative to petrochemical-based production. The hydroxycinnamic acid fraction of lignocellulosic biomass represents an untapped source of aromatic molecules that can be converted to numerous high-value products with industrial applications, including in the flavor and fragrance sector and pharmaceuticals. This review describes several biochemical pathways useful in the development of a biorefinery concept based on the biocatalytic conversion of the hydroxycinnamic acids ferulic, caffeic, and p-coumaric acid into high-value molecules. KEY POINTS: • The phenylpropanoids bioconversion pathways in the context of biorefineries • Description of pathways from hydroxycinnamic acids to high-value compounds • Metabolic engineering and synthetic biology advance hydroxycinnamic acid-based biorefineries.
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Affiliation(s)
- Robson Tramontina
- Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
- Programa de Processos Tecnológicos E Ambientais, Universidade de Sorocaba (UNISO), Sorocaba, São Paulo, Brazil
| | - Iara Ciancaglini
- Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
| | - Ellen K B Roman
- Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
| | - Micaela G Chacón
- Manchester Institute of Biotechnology (MIB), Department of Chemistry, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK
| | - Thamy L R Corrêa
- Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
| | - Neil Dixon
- Manchester Institute of Biotechnology (MIB), Department of Chemistry, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK
| | - Timothy D H Bugg
- Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK
| | - Fabio Marcio Squina
- Programa de Processos Tecnológicos E Ambientais, Universidade de Sorocaba (UNISO), Sorocaba, São Paulo, Brazil.
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8
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Meng L, Diao M, Wang Q, Peng L, Li J, Xie N. Efficient biosynthesis of resveratrol via combining phenylalanine and tyrosine pathways in Saccharomyces cerevisiae. Microb Cell Fact 2023; 22:46. [PMID: 36890537 PMCID: PMC9996981 DOI: 10.1186/s12934-023-02055-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Accepted: 03/04/2023] [Indexed: 03/10/2023] Open
Abstract
BACKGROUND Resveratrol is a commercially available stilbenoid widely used as dietary supplements, functional food ingredients, and cosmetic ingredients due to its diverse physiological activities. The production of resveratrol in microorganisms provides an ideal source that reduces the cost of resveratrol, but the titer in Saccharomyces cerevisiae was still much lower than that in other hosts. RESULTS To achieve enhanced production of resveratrol in S. cerevisiae, we constructed a biosynthetic pathway via combining phenylalanine and tyrosine pathways by introducing a bi-functional phenylalanine/tyrosine ammonia lyase from Rhodotorula toruloides. The combination of phenylalanine pathway with tyrosine pathway led to a 462% improvement of resveratrol production in yeast extract peptone dextrose (YPD) medium with 4% glucose, suggesting an alternative strategy for producing p-coumaric acid-derived compounds. Then the strains were further modified by integrating multi-copy biosynthetic pathway genes, improving metabolic flux to aromatic amino acids and malonyl-CoA, and deleting by-pathway genes, which resulted in 1155.0 mg/L resveratrol in shake flasks when cultured in YPD medium. Finally, a non-auxotrophic strain was tailored for resveratrol production in minimal medium without exogenous amino acid addition, and the highest resveratrol titer (4.1 g/L) ever reported was achieved in S. cerevisiae to our knowledge. CONCLUSIONS This study demonstrates the advantage of employing a bi-functional phenylalanine/tyrosine ammonia lyase in the biosynthetic pathway of resveratrol, suggesting an effective alternative in the production of p-coumaric acid-derived compounds. Moreover, the enhanced production of resveratrol in S. cerevisiae lays a foundation for constructing cell factories for various stilbenoids.
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Affiliation(s)
- Lijun Meng
- State Key Laboratory of NonFood Biomass and Enzyme Technology, Guangxi Key Laboratory of Bio-Refinery, National Engineering Research Center for Non-Food Biorefinery, Guangxi Biomass Engineering Technology Research Center, Guangxi Academy of Sciences, 98 Daling Road, Nanning, 530007, China.
| | - Mengxue Diao
- State Key Laboratory of NonFood Biomass and Enzyme Technology, Guangxi Key Laboratory of Bio-Refinery, National Engineering Research Center for Non-Food Biorefinery, Guangxi Biomass Engineering Technology Research Center, Guangxi Academy of Sciences, 98 Daling Road, Nanning, 530007, China
| | - Qingyan Wang
- State Key Laboratory of NonFood Biomass and Enzyme Technology, Guangxi Key Laboratory of Bio-Refinery, National Engineering Research Center for Non-Food Biorefinery, Guangxi Biomass Engineering Technology Research Center, Guangxi Academy of Sciences, 98 Daling Road, Nanning, 530007, China
| | - Longyun Peng
- State Key Laboratory of NonFood Biomass and Enzyme Technology, Guangxi Key Laboratory of Bio-Refinery, National Engineering Research Center for Non-Food Biorefinery, Guangxi Biomass Engineering Technology Research Center, Guangxi Academy of Sciences, 98 Daling Road, Nanning, 530007, China
| | - Jianxiu Li
- State Key Laboratory of NonFood Biomass and Enzyme Technology, Guangxi Key Laboratory of Bio-Refinery, National Engineering Research Center for Non-Food Biorefinery, Guangxi Biomass Engineering Technology Research Center, Guangxi Academy of Sciences, 98 Daling Road, Nanning, 530007, China
| | - Nengzhong Xie
- State Key Laboratory of NonFood Biomass and Enzyme Technology, Guangxi Key Laboratory of Bio-Refinery, National Engineering Research Center for Non-Food Biorefinery, Guangxi Biomass Engineering Technology Research Center, Guangxi Academy of Sciences, 98 Daling Road, Nanning, 530007, China.
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9
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Medicinal phytometabolites synthesis using yeast bioengineering platform. THE NUCLEUS 2022. [DOI: 10.1007/s13237-022-00396-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022] Open
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10
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Biotechnological production of specialty aromatic and aromatic-derivative compounds. World J Microbiol Biotechnol 2022; 38:80. [PMID: 35338395 DOI: 10.1007/s11274-022-03263-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 03/05/2022] [Indexed: 10/18/2022]
Abstract
Aromatic compounds are an important class of chemicals with different industrial applications. They are usually produced by chemical synthesis from petroleum-derived feedstocks, such as toluene, xylene and benzene. However, we are now facing threats from the excessive use of fossil fuels causing environmental problems such as global warming. Furthermore, fossil resources are not infinite, and will ultimately be depleted. To cope with these problems, the sustainable production of aromatic chemicals from renewable non-food biomass is urgent. With this in mind, the search for alternative methodologies to produce aromatic compounds using low-cost and environmentally friendly processes is becoming more and more important. Microorganisms are able to produce aromatic and aromatic-derivative compounds from sugar-based carbon sources. Metabolic engineering strategies as well as bioprocess optimization enable the development of microbial cell factories capable of efficiently producing aromatic compounds. This review presents current breakthroughs in microbial production of specialty aromatic and aromatic-derivative products, providing an overview on the general strategies and methodologies applied to build microbial cell factories for the production of these compounds. We present and describe some of the current challenges and gaps that must be overcome in order to render the biotechnological production of specialty aromatic and aromatic-derivative attractive and economically feasible at industrial scale.
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11
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Feng C, Chen J, Ye W, Liao K, Wang Z, Song X, Qiao M. Synthetic Biology-Driven Microbial Production of Resveratrol: Advances and Perspectives. Front Bioeng Biotechnol 2022; 10:833920. [PMID: 35127664 PMCID: PMC8811299 DOI: 10.3389/fbioe.2022.833920] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Accepted: 01/05/2022] [Indexed: 12/22/2022] Open
Abstract
Resveratrol, a bioactive natural product found in many plants, is a secondary metabolite and has attracted much attention in the medicine and health care products fields due to its remarkable biological activities including anti-cancer, anti-oxidation, anti-aging, anti-inflammation, neuroprotection and anti-glycation. However, traditional chemical synthesis and plant extraction methods are impractical for industrial resveratrol production because of low yield, toxic chemical solvents and environmental pollution during the production process. Recently, the biosynthesis of resveratrol by constructing microbial cell factories has attracted much attention, because it provides a safe and efficient route for the resveratrol production. This review discusses the physiological functions and market applications of resveratrol. In addition, recent significant biotechnology advances in resveratrol biosynthesis are systematically summarized. Furthermore, we discuss the current challenges and future prospects for strain development for large-scale resveratrol production at an industrial level.
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Affiliation(s)
- Chao Feng
- Department of Urology, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Jing Chen
- Department of Urology, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Wenxin Ye
- Department of Urology, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Kaisen Liao
- Department of Urology, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Zhanshi Wang
- Department of Urology, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Xiaofei Song
- The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China
- The Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China
- *Correspondence: Xiaofei Song, ; Mingqiang Qiao,
| | - Mingqiang Qiao
- The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China
- College of Life Sciences, Shanxi University, Taiyuan, China
- *Correspondence: Xiaofei Song, ; Mingqiang Qiao,
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12
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Heath RS, Ruscoe RE, Turner NJ. The beauty of biocatalysis: sustainable synthesis of ingredients in cosmetics. Nat Prod Rep 2021; 39:335-388. [PMID: 34879125 DOI: 10.1039/d1np00027f] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Covering: 2015 up to July 2021The market for cosmetics is consumer driven and the desire for green, sustainable and natural ingredients is increasing. The use of isolated enzymes and whole-cell organisms to synthesise these products is congruent with these values, especially when combined with the use of renewable, recyclable or waste feedstocks. The literature of biocatalysis for the synthesis of ingredients in cosmetics in the past five years is herein reviewed.
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Affiliation(s)
- Rachel S Heath
- Manchester Institute of Biotechnology, Department of Chemistry, University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
| | - Rebecca E Ruscoe
- Manchester Institute of Biotechnology, Department of Chemistry, University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
| | - Nicholas J Turner
- Manchester Institute of Biotechnology, Department of Chemistry, University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
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13
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Resveratrol Production in Yeast Hosts: Current Status and Perspectives. Biomolecules 2021; 11:biom11060830. [PMID: 34199540 PMCID: PMC8226833 DOI: 10.3390/biom11060830] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 05/29/2021] [Accepted: 05/30/2021] [Indexed: 12/14/2022] Open
Abstract
Resveratrol is a plant secondary metabolite known for its therapeutic applications as an antioxidant, anti-cancer, anti-inflammatory, anti-aging, cardio-protective, and neuroprotective agent. Topical formulas of resveratrol are also used for skin disease management and in cosmetic industries. Due to its importance, high resveratrol production is urgently required. Since the last decade, intensive efforts have been devoted to obtaining resveratrol from microorganisms by pathway and metabolic engineering. Yeasts were proven to be excellent host candidates for resveratrol production. In addition to the similar intracellular compartments between yeasts and plants, yeasts exhibit the ability to express genes coding for plant-derived enzymes and to perform post-translational modification. Therefore, this review summarizes the attempts to use yeasts as a platform for resveratrol synthesis as the next promising route in producing high titers of resveratrol from genetically engineered strains.
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14
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Jeandet P, Vannozzi A, Sobarzo-Sánchez E, Uddin MS, Bru R, Martínez-Márquez A, Clément C, Cordelier S, Manayi A, Nabavi SF, Rasekhian M, El-Saber Batiha G, Khan H, Morkunas I, Belwal T, Jiang J, Koffas M, Nabavi SM. Phytostilbenes as agrochemicals: biosynthesis, bioactivity, metabolic engineering and biotechnology. Nat Prod Rep 2021; 38:1282-1329. [PMID: 33351014 DOI: 10.1039/d0np00030b] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Covering: 1976 to 2020. Although constituting a limited chemical family, phytostilbenes represent an emblematic group of molecules among natural compounds. Ever since their discovery as antifungal compounds in plants and their ascribed role in human health and disease, phytostilbenes have never ceased to arouse interest for researchers, leading to a huge development of the literature in this field. Owing to this, the number of references to this class of compounds has reached the tens of thousands. The objective of this article is thus to offer an overview of the different aspects of these compounds through a large bibliography analysis of more than 500 articles. All the aspects regarding phytostilbenes will be covered including their chemistry and biochemistry, regulation of their biosynthesis, biological activities in plants, molecular engineering of stilbene pathways in plants and microbes as well as their biotechnological production by plant cell systems.
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Affiliation(s)
- Philippe Jeandet
- Research Unit "Induced Resistance and Plant Bioprotection", EA 4707, SFR Condorcet FR CNRS 3417, Faculty of Sciences, University of Reims Champagne-Ardenne, PO Box 1039, 51687 Reims Cedex 2, France.
| | - Alessandro Vannozzi
- Department of Agronomy, Food, Natural Resources, Animals, and Environment (DAFNAE), University of Padova, 35020 Legnaro, PD, Italy
| | - Eduardo Sobarzo-Sánchez
- Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, Campus Vida, 15782 Santiago de Compostela, Spain and Instituto de Investigación e Innovación en Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, Chile
| | - Md Sahab Uddin
- Department of Pharmacy, Southeast University, Dhaka, Bangladesh and Neuroscience Research Network, Dhaka, Bangladesh
| | - Roque Bru
- Plant Proteomics and Functional Genomics Group, Department of Agrochemistry and Biochemistry, Faculty of Science, University of Alicante, Alicante, Spain
| | - Ascension Martínez-Márquez
- Plant Proteomics and Functional Genomics Group, Department of Agrochemistry and Biochemistry, Faculty of Science, University of Alicante, Alicante, Spain
| | - Christophe Clément
- Research Unit "Induced Resistance and Plant Bioprotection", EA 4707, SFR Condorcet FR CNRS 3417, Faculty of Sciences, University of Reims Champagne-Ardenne, PO Box 1039, 51687 Reims Cedex 2, France.
| | - Sylvain Cordelier
- Research Unit "Induced Resistance and Plant Bioprotection", EA 4707, SFR Condorcet FR CNRS 3417, Faculty of Sciences, University of Reims Champagne-Ardenne, PO Box 1039, 51687 Reims Cedex 2, France.
| | - Azadeh Manayi
- Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, 1417614411 Tehran, Iran
| | - Seyed Fazel Nabavi
- Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran 14359-16471, Iran
| | - Mahsa Rasekhian
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt
| | - Haroon Khan
- Department of Pharmacy, Faculty of Chemical and Life Sciences, Abdul Wali Khan University Mardan, 23200, Pakistan
| | - Iwona Morkunas
- Department of Plant Physiology, Poznań University of Life Sciences, Wołyńska 35, 60-637 Poznań, Poland
| | - Tarun Belwal
- Zhejiang University, College of Biosystems Engineering and Food Science, Key Laboratory of Agro-Products Postharvest Handling of Ministry of Agriculture and Rural Affairs, Zhejiang Key Laboratory for Agri-Food Processing, Hangzhou 310058, The People's Republic of China
| | - Jingjie Jiang
- Dorothy and Fred Chau '71 Constellation Professor, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Room 4005D, 110 8th Street, Troy, NY 12180, USA
| | - Mattheos Koffas
- Dorothy and Fred Chau '71 Constellation Professor, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Room 4005D, 110 8th Street, Troy, NY 12180, USA
| | - Seyed Mohammad Nabavi
- Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran 14359-16471, Iran
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15
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Lahue C, Madden AA, Dunn RR, Smukowski Heil C. History and Domestication of Saccharomyces cerevisiae in Bread Baking. Front Genet 2020; 11:584718. [PMID: 33262788 PMCID: PMC7686800 DOI: 10.3389/fgene.2020.584718] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Accepted: 10/13/2020] [Indexed: 11/30/2022] Open
Abstract
The yeast Saccharomyces cerevisiae has been instrumental in the fermentation of foods and beverages for millennia. In addition to fermentations like wine, beer, cider, sake, and bread, S. cerevisiae has been isolated from environments ranging from soil and trees, to human clinical isolates. Each of these environments has unique selection pressures that S. cerevisiae must adapt to. Bread dough, for example, requires S. cerevisiae to efficiently utilize the complex sugar maltose; tolerate osmotic stress due to the semi-solid state of dough, high salt, and high sugar content of some doughs; withstand various processing conditions, including freezing and drying; and produce desirable aromas and flavors. In this review, we explore the history of bread that gave rise to modern commercial baking yeast, and the genetic and genomic changes that accompanied this. We illustrate the genetic and phenotypic variation that has been documented in baking strains and wild strains, and how this variation might be used for baking strain improvement. While we continue to improve our understanding of how baking strains have adapted to bread dough, we conclude by highlighting some of the remaining open questions in the field.
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Affiliation(s)
- Caitlin Lahue
- Department of Biological Sciences, North Carolina State University, Raleigh, NC, United States
- Department of Applied Ecology, North Carolina State University, Raleigh, NC, United States
| | - Anne A. Madden
- Department of Applied Ecology, North Carolina State University, Raleigh, NC, United States
| | - Robert R. Dunn
- Department of Applied Ecology, North Carolina State University, Raleigh, NC, United States
- Center for Evolutionary Hologenomics, The GLOBE Institute, University of Copenhagen, Copenhagen, Denmark
| | - Caiti Smukowski Heil
- Department of Biological Sciences, North Carolina State University, Raleigh, NC, United States
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16
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Bradley SA, Zhang J, Jensen MK. Deploying Microbial Synthesis for Halogenating and Diversifying Medicinal Alkaloid Scaffolds. Front Bioeng Biotechnol 2020; 8:594126. [PMID: 33195162 PMCID: PMC7644825 DOI: 10.3389/fbioe.2020.594126] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Accepted: 10/02/2020] [Indexed: 11/13/2022] Open
Abstract
Plants produce some of the most potent therapeutics and have been used for thousands of years to treat human diseases. Today, many medicinal natural products are still extracted from source plants at scale as their complexity precludes total synthesis from bulk chemicals. However, extraction from plants can be an unreliable and low-yielding source for human therapeutics, making the supply chain for some of these life-saving medicines expensive and unstable. There has therefore been significant interest in refactoring these plant pathways in genetically tractable microbes, which grow more reliably and where the plant pathways can be more easily engineered to improve the titer, rate and yield of medicinal natural products. In addition, refactoring plant biosynthetic pathways in microbes also offers the possibility to explore new-to-nature chemistry more systematically, and thereby help expand the chemical space that can be probed for drugs as well as enable the study of pharmacological properties of such new-to-nature chemistry. This perspective will review the recent progress toward heterologous production of plant medicinal alkaloids in microbial systems. In particular, we focus on the refactoring of halogenated alkaloids in yeast, which has created an unprecedented opportunity for biosynthesis of previously inaccessible new-to-nature variants of the natural alkaloid scaffolds.
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Affiliation(s)
| | | | - Michael K. Jensen
- Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark
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17
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Liu J, Zhang X, Yan T, Wang F, Li J, Jia L, Jia J, Hu G. Screening of an Endophyte Transforming Polydatin to Resveratrol from Reynoutria Japonica Houtt and the Optimization of Its Transformation Parameters. Molecules 2020; 25:E4830. [PMID: 33092209 PMCID: PMC7587952 DOI: 10.3390/molecules25204830] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 09/28/2020] [Accepted: 10/14/2020] [Indexed: 12/13/2022] Open
Abstract
Resveratrol showed various kinds of bioactivities, such as antioxidant, antimicrobial, anticancer effects and, therefore, has been used widely as an important ingredient in medication, healthy foods and cosmetics. However, in nature, resveratrol usually exists at low content and more often exists as polydatin. Therefore, it becomes important to find the cost-effective and environmental-friendly way to transform polydatin to resveratrol. In this study, endophytes were isolated from the rhizome tissue of Reynoutria japonica and screened for transforming polydatin to resveratrol using reversed-phase high-performance liquid chromatography (RP-HPLC) and confirmed by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy. A bacterium identified as Bacillus aryabhattai using 16S rRNA phylogenetic tree analysis showed highest transformation rate. The transforming conditions were optimized including substrate concentration, substrate addition time, culture temperature and inoculation ratio. Our results demonstrated that the bacteria isolated from R. japonica rhizome tissue showed high activity in transforming polydatin into resveratrol. Crude extract of R. japonica root and rhizome (RJE) was also tested as substrate and it was found that the transformation was significantly inhibited at 10.0 mg/mL RJE. Emodin at equivalent concentration of 10.0 mg/mL RJE showed no inhibition activity, and glucose content in RJE was trace and far from enough to exhibit the inhibitory activity. Successive solvent partition followed by an inhibition activity assay revealed that the ethyl acetate fraction showed the main inhibition activity. However, due to the coexistence of polydatin and compounds with inhibitory activity, the concentration of RJE can only be used at limited concentration as substrate.
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Affiliation(s)
- Jin Liu
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China; (J.L.); (X.Z.); (T.Y.); (F.W.); (J.L.); (L.J.); (J.J.)
| | - Xueqing Zhang
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China; (J.L.); (X.Z.); (T.Y.); (F.W.); (J.L.); (L.J.); (J.J.)
| | - Ting Yan
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China; (J.L.); (X.Z.); (T.Y.); (F.W.); (J.L.); (L.J.); (J.J.)
| | - Faling Wang
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China; (J.L.); (X.Z.); (T.Y.); (F.W.); (J.L.); (L.J.); (J.J.)
| | - Jing Li
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China; (J.L.); (X.Z.); (T.Y.); (F.W.); (J.L.); (L.J.); (J.J.)
| | - Lingyun Jia
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China; (J.L.); (X.Z.); (T.Y.); (F.W.); (J.L.); (L.J.); (J.J.)
| | - Jingming Jia
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China; (J.L.); (X.Z.); (T.Y.); (F.W.); (J.L.); (L.J.); (J.J.)
- China-Korea Joint Laboratory of Molecular Pharmacognosy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Gaosheng Hu
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China; (J.L.); (X.Z.); (T.Y.); (F.W.); (J.L.); (L.J.); (J.J.)
- China-Korea Joint Laboratory of Molecular Pharmacognosy, Shenyang Pharmaceutical University, Shenyang 110016, China
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18
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Next Generation Winemakers: Genetic Engineering in Saccharomyces cerevisiae for Trendy Challenges. Bioengineering (Basel) 2020; 7:bioengineering7040128. [PMID: 33066502 PMCID: PMC7712467 DOI: 10.3390/bioengineering7040128] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 10/08/2020] [Accepted: 10/13/2020] [Indexed: 02/06/2023] Open
Abstract
The most famous yeast of all, Saccharomyces cerevisiae, has been used by humankind for at least 8000 years, to produce bread, beer and wine, even without knowing about its existence. Only in the last century we have been fully aware of the amazing power of this yeast not only for ancient uses but also for biotechnology purposes. In the last decades, wine culture has become and more demanding all over the world. By applying as powerful a biotechnological tool as genetic engineering in S. cerevisiae, new horizons appear to develop fresh, improved, or modified wine characteristics, properties, flavors, fragrances or production processes, to fulfill an increasingly sophisticated market that moves around 31.4 billion € per year.
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19
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Chrzanowski G. Saccharomyces Cerevisiae-An Interesting Producer of Bioactive Plant Polyphenolic Metabolites. Int J Mol Sci 2020; 21:ijms21197343. [PMID: 33027901 PMCID: PMC7582661 DOI: 10.3390/ijms21197343] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 09/28/2020] [Accepted: 09/29/2020] [Indexed: 12/20/2022] Open
Abstract
Secondary phenolic metabolites are defined as valuable natural products synthesized by different organisms that are not essential for growth and development. These compounds play an essential role in plant defense mechanisms and an important role in the pharmaceutical, cosmetics, food, and agricultural industries. Despite the vast chemical diversity of natural compounds, their content in plants is very low, and, as a consequence, this eliminates the possibility of the production of these interesting secondary metabolites from plants. Therefore, microorganisms are widely used as cell factories by industrial biotechnology, in the production of different non-native compounds. Among microorganisms commonly used in biotechnological applications, yeast are a prominent host for the diverse secondary metabolite biosynthetic pathways. Saccharomyces cerevisiae is often regarded as a better host organism for the heterologous production of phenolic compounds, particularly if the expression of different plant genes is necessary.
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Affiliation(s)
- Grzegorz Chrzanowski
- Department of Biotechnology, Institute of Biology and Biotechnology, University of Rzeszow, 35-310 Rzeszow, Poland
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20
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Optimization of an abiotic elicitor (ultrasound) treatment conditions on trans-resveratrol production from Kalecik Karası ( Vitis vinifera L.) grape skin. Journal of Food Science and Technology 2020; 58:2121-2132. [PMID: 33967310 DOI: 10.1007/s13197-020-04722-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Revised: 05/25/2020] [Accepted: 08/13/2020] [Indexed: 12/19/2022]
Abstract
Grapes are known to synthesize resveratrol, a stilbene phytoalexin, associated with cancer chemopreventive activity and cardioprotection. The effect of ultrasound (US) abiotic elicitor treatments on trans-resveratrol content in Kalecik Karası fresh and frozen grape skin was determined. D-optimal point change design was used under RSM for the experimental design of US treatment. The optimization was solved with the help of the Pareto areas and the optimal input variable values were determined by the desirability function with fuzzy similar perceivable ratio method. The optimum conditions of US treatment for fresh grape skin were determined as follows: incubation time-24 h, US application method-(P01), US frequency-20 kHz, US treatment time-60 min and ultrasonic intensity (UI)-1.15 W cm-2. The trans-resveratrol content (0.18 ± 0.01 mg/g) in the untreated grape skin significantly increased with optimum US treatment (3.58 ± 0.08 mg/g), increasing production to 19.9 times.
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21
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Eldarov MA, Mardanov AV. Metabolic Engineering of Wine Strains of Saccharomyces cerevisiae. Genes (Basel) 2020; 11:E964. [PMID: 32825346 PMCID: PMC7565949 DOI: 10.3390/genes11090964] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 08/16/2020] [Accepted: 08/18/2020] [Indexed: 01/26/2023] Open
Abstract
Modern industrial winemaking is based on the use of starter cultures of specialized wine strains of Saccharomyces cerevisiae yeast. Commercial wine strains have a number of advantages over natural isolates, and it is their use that guarantees the stability and reproducibility of industrial winemaking technologies. For the highly competitive wine market with new demands for improved wine quality, it has become increasingly critical to develop new wine strains and winemaking technologies. Novel opportunities for precise wine strain engineering based on detailed knowledge of the molecular nature of a particular trait or phenotype have recently emerged due to the rapid progress in genomic and "postgenomic" studies with wine yeast strains. The review summarizes the current achievements of the metabolic engineering of wine yeast, the results of recent studies and the prospects for the application of genomic editing technologies for improving wine S. cerevisiae strains.
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Affiliation(s)
| | - Andrey V. Mardanov
- Institute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences, 119071 Moscow, Russia;
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22
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Kontaxakis E, Trantas E, Ververidis F. Resveratrol: A Fair Race Towards Replacing Sulfites in Wines. Molecules 2020; 25:E2378. [PMID: 32443913 PMCID: PMC7288175 DOI: 10.3390/molecules25102378] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 05/12/2020] [Accepted: 05/13/2020] [Indexed: 12/24/2022] Open
Abstract
In recent years, significant efforts to produce healthier wines has led to the replacement or reduction of the addition of sulfites, using alternative substances or techniques. Resveratrol and related biophenols seem to be of great interest, since beyond their protective nature and contrary to sulfites they can positively affect consumer health. These bioactive phytochemicals are naturally produced in grapes as evolutionary acquired mechanisms against pathogens and UV irradiation. However, despite the efforts made so far attempting to develop economic and industrially adopted isolation techniques, available quantities of these biophenols for commercial use are still quite limited. Therefore, such molecules are still not able to meet the needs of industrial use due to their prohibitive marketable cost. In this review we summarize the efforts that have been made to biosynthesize these molecules through alternative, innovative ways. Increasing interest in modern biotechnological approaches has shed light on the exploitation of metabolically engineered microbial factories, instead of plants, to produce molecules of industrial interest. Such approaches, also reviewed here, are expected to lower the cost and appear promising to produce enough surplus to attract further oenological experimentation upon yielding functional wines. This development is expected to attract further industrial attention, continuing the race to partially or totally replace the external addition of sulfites. We also review important physicochemical properties of resveratrol in relation to enriching wines.
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Affiliation(s)
| | | | - Filippos Ververidis
- Plant Biochemistry and Biotechnology Group, Laboratory of Biological and Biotechnological Applications, Department of Agriculture, School of Agricultural Sciences, Hellenic Mediterranean University, GR 710 04 Heraklion, Greece; (E.K.); (E.T.)
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23
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Long-Term Adaption to High Osmotic Stress as a Tool for Improving Enological Characteristics in Industrial Wine Yeast. Genes (Basel) 2020; 11:genes11050576. [PMID: 32443892 PMCID: PMC7288280 DOI: 10.3390/genes11050576] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 05/15/2020] [Accepted: 05/18/2020] [Indexed: 12/28/2022] Open
Abstract
Industrial wine yeasts owe their adaptability in constantly changing environments to a long evolutionary history that combines naturally occurring evolutionary events with human-enforced domestication. Among the many stressors associated with winemaking processes that have potentially detrimental impacts on yeast viability, growth, and fermentation performance are hyperosmolarity, high glucose concentrations at the beginning of fermentation, followed by the depletion of nutrients at the end of this process. Therefore, in this study, we subjected three widely used industrial wine yeasts to adaptive laboratory evolution under potassium chloride (KCl)-induced osmotic stress. At the end of the evolutionary experiment, we evaluated the tolerance to high osmotic stress of the evolved strains. All of the analyzed strains improved their fitness under high osmotic stress without worsening their economic characteristics, such as growth rate and viability. The evolved derivatives of two strains also gained the ability to accumulate glycogen, a readily mobilized storage form of glucose conferring enhanced viability and vitality of cells during prolonged nutrient deprivation. Moreover, laboratory-scale fermentation in grape juice showed that some of the KCl-evolved strains significantly enhanced glycerol synthesis and production of resveratrol-enriched wines, which in turn greatly improved the wine sensory profile. Altogether, these findings showed that long-term adaptations to osmotic stress can be an attractive approach to develop industrial yeasts.
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24
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Shen YP, Niu FX, Yan ZB, Fong LS, Huang YB, Liu JZ. Recent Advances in Metabolically Engineered Microorganisms for the Production of Aromatic Chemicals Derived From Aromatic Amino Acids. Front Bioeng Biotechnol 2020; 8:407. [PMID: 32432104 PMCID: PMC7214760 DOI: 10.3389/fbioe.2020.00407] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 04/14/2020] [Indexed: 12/16/2022] Open
Abstract
Aromatic compounds derived from aromatic amino acids are an important class of diverse chemicals with a wide range of industrial and commercial applications. They are currently produced via petrochemical processes, which are not sustainable and eco-friendly. In the past decades, significant progress has been made in the construction of microbial cell factories capable of effectively converting renewable carbon sources into value-added aromatics. Here, we systematically and comprehensively review the recent advancements in metabolic engineering and synthetic biology in the microbial production of aromatic amino acid derivatives, stilbenes, and benzylisoquinoline alkaloids. The future outlook concerning the engineering of microbial cell factories for the production of aromatic compounds is also discussed.
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Affiliation(s)
- Yu-Ping Shen
- Guangdong Province Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals, Biomedical Center, School of Life Sciences, Institute of Synthetic Biology, Sun Yat-sen University, Guangzhou, China
| | - Fu-Xing Niu
- Guangdong Province Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals, Biomedical Center, School of Life Sciences, Institute of Synthetic Biology, Sun Yat-sen University, Guangzhou, China
| | - Zhi-Bo Yan
- Guangdong Province Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals, Biomedical Center, School of Life Sciences, Institute of Synthetic Biology, Sun Yat-sen University, Guangzhou, China
| | - Lai San Fong
- Guangdong Province Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals, Biomedical Center, School of Life Sciences, Institute of Synthetic Biology, Sun Yat-sen University, Guangzhou, China
| | - Yuan-Bin Huang
- Guangdong Province Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals, Biomedical Center, School of Life Sciences, Institute of Synthetic Biology, Sun Yat-sen University, Guangzhou, China
| | - Jian-Zhong Liu
- Guangdong Province Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals, Biomedical Center, School of Life Sciences, Institute of Synthetic Biology, Sun Yat-sen University, Guangzhou, China
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25
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Rainha J, Gomes D, Rodrigues LR, Rodrigues JL. Synthetic Biology Approaches to Engineer Saccharomyces cerevisiae towards the Industrial Production of Valuable Polyphenolic Compounds. Life (Basel) 2020; 10:life10050056. [PMID: 32370107 PMCID: PMC7281501 DOI: 10.3390/life10050056] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 04/22/2020] [Accepted: 04/30/2020] [Indexed: 12/27/2022] Open
Abstract
Polyphenols are plant secondary metabolites with diverse biological and potential therapeutic activities such as antioxidant, anti-inflammatory and anticancer, among others. However, their extraction from the native plants is not enough to satisfy the increasing demand for this type of compounds. The development of microbial cell factories to effectively produce polyphenols may represent the most attractive solution to overcome this limitation and produce high amounts of these bioactive molecules. With the advances in the synthetic biology field, the development of efficient microbial cell factories has become easier, largely due to the development of the molecular biology techniques and by the identification of novel isoenzymes in plants or simpler organisms to construct the heterologous pathways. Furthermore, efforts have been made to make the process more profitable through improvements in the host chassis. In this review, advances in the production of polyphenols by genetically engineered Saccharomyces cerevisiae as well as by synthetic biology and metabolic engineering approaches to improve the production of these compounds at industrial settings are discussed.
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26
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Abstract
Metabolic engineering aims to produce chemicals of interest from living organisms, to advance toward greener chemistry. Despite efforts, the research and development process is still long and costly, and efficient computational design tools are required to explore the chemical biosynthetic space. Here, we propose to explore the bioretrosynthesis space using an artificial intelligence based approach relying on the Monte Carlo Tree Search reinforcement learning method, guided by chemical similarity. We implement this method in RetroPath RL, an open-source and modular command line tool. We validate it on a golden data set of 20 manually curated experimental pathways as well as on a larger data set of 152 successful metabolic engineering projects. Moreover, we provide a novel feature that suggests potential media supplements to complement the enzymatic synthesis plan.
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Affiliation(s)
- Mathilde Koch
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France
| | - Thomas Duigou
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France
| | - Jean-Loup Faulon
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France
- iSSB Laboratory, Génomique Métabolique, Genoscope, Institut François Jacob, CEA, CNRS, Univ Evry, Université Paris-Saclay, 91057 Evry, France
- SYNBIOCHEM Center, School of Chemistry, University of Manchester, Manchester M13 9PL, U.K
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Engineering a microbial biosynthesis platform for de novo production of tropane alkaloids. Nat Commun 2019; 10:3634. [PMID: 31406117 PMCID: PMC6690885 DOI: 10.1038/s41467-019-11588-w] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 07/18/2019] [Indexed: 02/07/2023] Open
Abstract
Tropane alkaloids (TAs) are a class of phytochemicals produced by plants of the nightshade family used for treating diverse neurological disorders. Here, we demonstrate de novo production of tropine, a key intermediate in the biosynthetic pathway of medicinal TAs such as scopolamine, from simple carbon and nitrogen sources in yeast (Saccharomyces cerevisiae). Our engineered strain incorporates 15 additional genes, including 11 derived from diverse plants and bacteria, and 7 disruptions to yeast regulatory or biosynthetic proteins to produce tropine at titers of 6 mg/L. We also demonstrate the utility of our engineered yeast platform for the discovery of TA derivatives by combining biosynthetic modules from distant plant lineages to achieve de novo production of cinnamoyltropine, a non-canonical TA. Our engineered strain constitutes a starting point for future optimization efforts towards realizing industrial fermentation of medicinal TAs and a platform for the synthesis of TA derivatives with enhanced bioactivities. Tropane alkaloids (TAs) are a group of phytochemicals that are used to treat neurological disorders. Here, the authors engineer baker’s yeast to produce tropine, a key intermediate in the biosynthetic pathway of TAs, and cinnamoyltropine, a non-canonical TA, from simple carbon and nitrogen sources.
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28
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Biotechnological Advances in Resveratrol Production and its Chemical Diversity. Molecules 2019; 24:molecules24142571. [PMID: 31311182 PMCID: PMC6680439 DOI: 10.3390/molecules24142571] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 07/01/2019] [Indexed: 12/14/2022] Open
Abstract
The very well-known bioactive natural product, resveratrol (3,5,4'-trihydroxystilbene), is a highly studied secondary metabolite produced by several plants, particularly grapes, passion fruit, white tea, and berries. It is in high demand not only because of its wide range of biological activities against various kinds of cardiovascular and nerve-related diseases, but also as important ingredients in pharmaceuticals and nutritional supplements. Due to its very low content in plants, multi-step isolation and purification processes, and environmental and chemical hazards issues, resveratrol extraction from plants is difficult, time consuming, impracticable, and unsustainable. Therefore, microbial hosts, such as Escherichia coli, Saccharomyces cerevisiae, and Corynebacterium glutamicum, are commonly used as an alternative production source by improvising resveratrol biosynthetic genes in them. The biosynthesis genes are rewired applying combinatorial biosynthetic systems, including metabolic engineering and synthetic biology, while optimizing the various production processes. The native biosynthesis of resveratrol is not present in microbes, which are easy to manipulate genetically, so the use of microbial hosts is increasing these days. This review will mainly focus on the recent biotechnological advances for the production of resveratrol, including the various strategies used to produce its chemically diverse derivatives.
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29
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30
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Kores K, Lešnik S, Bren U, Janežič D, Konc J. Discovery of Novel Potential Human Targets of Resveratrol by Inverse Molecular Docking. J Chem Inf Model 2019; 59:2467-2478. [PMID: 30883115 DOI: 10.1021/acs.jcim.8b00981] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Resveratrol is a polyphenol known for its antioxidant and anti-inflammatory properties, which support its use as a treatment for variety of diseases. There are already known connections of resveratrol to chemoprevention of cancer because of its ability to prevent tumor initiation and inhibit tumor promotion and progression. Resveratrol is also believed to be important in cardiovascular diseases and neurological disorders, such as Alzheimer's disease. Using an inverse molecular docking approach, we sought to find new potential targets of resveratrol. Docking of resveratrol into each ProBiS predicted binding site of >38 000 protein structures from the Protein Data Bank was examined, and a number of novel potential targets into which resveratrol was docked successfully were found. These explain known actions or predict new effects of resveratrol. The results included three human proteins that are already known to bind resveratrol. A majority of proteins discovered however have no already described connections with resveratrol. We report new potential target human proteins and proteins connected with different organisms into which resveratrol can dock. Our results reveal previously unknown potential target human proteins, whose connection with cardiovascular and neurological disorders could lead to new potential treatments for variety of diseases. We believe that our research could help in future experimental studies on revestratol bioactivity in humans.
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Affiliation(s)
- Katarina Kores
- University of Maribor , Faculty for Chemistry and Chemical Technology Maribor , Smetanova ulica 17 , SI-2000 Maribor , Slovenia
| | - Samo Lešnik
- National Institute of Chemistry , Hajdrihova 19 , SI-1000 Ljubljana , Slovenia
| | - Urban Bren
- University of Maribor , Faculty for Chemistry and Chemical Technology Maribor , Smetanova ulica 17 , SI-2000 Maribor , Slovenia.,National Institute of Chemistry , Hajdrihova 19 , SI-1000 Ljubljana , Slovenia.,University of Primorska , Faculty of Mathematics, Natural Sciences and Information Technology , Glagoljaška 8 , SI-6000 Koper , Slovenia
| | - Dušanka Janežič
- University of Primorska , Faculty of Mathematics, Natural Sciences and Information Technology , Glagoljaška 8 , SI-6000 Koper , Slovenia
| | - Janez Konc
- National Institute of Chemistry , Hajdrihova 19 , SI-1000 Ljubljana , Slovenia.,University of Primorska , Faculty of Mathematics, Natural Sciences and Information Technology , Glagoljaška 8 , SI-6000 Koper , Slovenia
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31
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Huccetogullari D, Luo ZW, Lee SY. Metabolic engineering of microorganisms for production of aromatic compounds. Microb Cell Fact 2019; 18:41. [PMID: 30808357 PMCID: PMC6390333 DOI: 10.1186/s12934-019-1090-4] [Citation(s) in RCA: 117] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Accepted: 02/19/2019] [Indexed: 01/09/2023] Open
Abstract
Metabolic engineering has been enabling development of high performance microbial strains for the efficient production of natural and non-natural compounds from renewable non-food biomass. Even though microbial production of various chemicals has successfully been conducted and commercialized, there are still numerous chemicals and materials that await their efficient bio-based production. Aromatic chemicals, which are typically derived from benzene, toluene and xylene in petroleum industry, have been used in large amounts in various industries. Over the last three decades, many metabolically engineered microorganisms have been developed for the bio-based production of aromatic chemicals, many of which are derived from aromatic amino acid pathways. This review highlights the latest metabolic engineering strategies and tools applied to the biosynthesis of aromatic chemicals, many derived from shikimate and aromatic amino acids, including L-phenylalanine, L-tyrosine and L-tryptophan. It is expected that more and more engineered microorganisms capable of efficiently producing aromatic chemicals will be developed toward their industrial-scale production from renewable biomass.
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Affiliation(s)
- Damla Huccetogullari
- Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program) and Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea
- Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST, Daejeon, 34141, Republic of Korea
| | - Zi Wei Luo
- Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program) and Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea
- Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST, Daejeon, 34141, Republic of Korea
| | - Sang Yup Lee
- Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program) and Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
- Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST, Daejeon, 34141, Republic of Korea.
- BioProcess Engineering Research Center and Bioinformatics Research Center, KAIST, Daejeon, 34141, Republic of Korea.
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32
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The Effects of Resveratrol in the Treatment of Metabolic Syndrome. Int J Mol Sci 2019; 20:ijms20030535. [PMID: 30695995 PMCID: PMC6387422 DOI: 10.3390/ijms20030535] [Citation(s) in RCA: 86] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Revised: 01/22/2019] [Accepted: 01/24/2019] [Indexed: 12/22/2022] Open
Abstract
Resveratrol, also known as 3,5,4′-trihydroxystilbene, is a natural polyphenol that occurs as a phytoalexin. It is produced by plant sources such as grapes, apples, blueberries, plums, peanuts, and other oilseeds. This compound has a variety of effects on human health and diseases. This review summarizes the mounting evidence that resveratrol is helpful in treating metabolic syndrome and related disorders. Resveratrol can be provided either early as a reprogramming agent or later as part of treatment. A few of the main mechanisms underlying the beneficial effects of resveratrol on metabolic syndrome are outlined. This review also discusses the potential of resveratrol derivatives as a complementary or alternative medicine. In conclusion, resveratrol could be a useful regimen for the prevention and treatment of metabolic syndrome and its related conditions.
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33
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Resveratrol: from enhanced biosynthesis and bioavailability to multitargeting chronic diseases. Biomed Pharmacother 2018; 109:2237-2251. [PMID: 30551481 DOI: 10.1016/j.biopha.2018.11.075] [Citation(s) in RCA: 157] [Impact Index Per Article: 22.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 11/13/2018] [Accepted: 11/19/2018] [Indexed: 12/17/2022] Open
Abstract
Resveratrol, a phytoalexin with a wide range of pharmacological properties is synthesised by plants in response to stress, injury, infection or UV radiations. As it is a secondary metabolite with many health promoting properties, various methods employing microorganisms and genetic manipulation of different synthetic enzymes, have been comprehensively studied to increase its production. Its rapid metabolism and low bioavailability have been addressed by the use of bio enhancers and nano-formulations. This flavonoid is extensively researched due to its pharmacological properties such as anti-oxidative, anti-inflammatory and immuno-modulating effects. Knowledge of these properties of resveratrol has led to elaborate studies on its effect on diabetes, neurodegenerative diseases, cancer, ageing, obesity and cardiovascular diseases. At molecular level it targets sirtuin, adenosine monophosphate kinase, nuclear Factor-κB, inflammatory cytokines, anti-oxidant enzymes along with cellular processes such as angiogenesis, apoptosis, mitochondrial biogenesis, gluconeogenesis and lipid metabolism. This review discusses the properties of resveratrol and the different approaches of addressing the unfavourable synthesis and pharmacokinetics of this stilbene. Pre-clinical evaluations of resveratrol on diabetes mellitus, cardiovascular and neurological diseases are elaborately discussed and the underlying pathways involved in its therapeutic activity have been given paramount importance. Following the pre-clinical studies, clinical trials on the same reveal the efficacy of resveratrol in the effective management of these diseases. This review provides an intricate insight on resveratrol's significance from a dietary component to a therapeutic agent.
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34
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Palmer CM, Alper HS. Expanding the Chemical Palette of Industrial Microbes: Metabolic Engineering for Type III PKS-Derived Polyketides. Biotechnol J 2018; 14:e1700463. [DOI: 10.1002/biot.201700463] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Revised: 10/18/2018] [Indexed: 11/07/2022]
Affiliation(s)
- Claire M. Palmer
- Institute for Cellular and Molecular Biology; The University of Texas at Austin; Austin 200 E Dean Keeton St. Stop C0400 Austin TX 78712
| | - Hal S. Alper
- Institute for Cellular and Molecular Biology; The University of Texas at Austin; Austin 200 E Dean Keeton St. Stop C0400 Austin TX 78712
- McKetta Department of Chemical Engineering; The University of Texas at Austin; Austin 200 E Dean Keeton St. Stop C0400 Austin TX 78712
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35
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Engineering stilbene metabolic pathways in microbial cells. Biotechnol Adv 2018; 36:2264-2283. [PMID: 30414914 DOI: 10.1016/j.biotechadv.2018.11.002] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 11/07/2018] [Accepted: 11/07/2018] [Indexed: 02/06/2023]
Abstract
Numerous in vitro and in vivo studies on biological activities of phytostilbenes have brought to the fore the remarkable properties of these compounds and their derivatives, making them a top storyline in natural product research fields. However, getting stilbenes in sufficient amounts for routine biological activity studies and make them available for pharmaceutical and/or nutraceutical industry applications, is hampered by the difficulty to source them through synthetic chemistry-based pathways or extraction from the native plants. Hence, microbial cell cultures have rapidly became potent workhorse factories for stilbene production. In this review, we present the combined efforts made during the past 15 years to engineer stilbene metabolic pathways in microbial cells, mainly the Saccharomyces cerevisiae baker yeast, the Escherichia coli and the Corynebacterium glutamicum bacteria. Rationalized approaches to the heterologous expression of the partial or the entire stilbene biosynthetic routes are presented to allow the identification and/or bypassing of the major bottlenecks in the endogenous microbial cell metabolism as well as potential regulations of the genes involved in these metabolic pathways. The contributions of bioinformatics to synthetic biology are developed to highlight their tremendous help in predicting which target genes are likely to be up-regulated or deleted for controlling the dynamics of precursor flows in the tailored microbial cells. Further insight is given to the metabolic engineering of microbial cells with "decorating" enzymes, such as methyl and glycosyltransferases or hydroxylases, which can act sequentially on the stilbene core structure. Altogether, the cellular optimization of stilbene biosynthetic pathways integrating more and more complex constructs up to twelve genetic modifications has led to stilbene titers ranging from hundreds of milligrams to the gram-scale yields from various carbon sources. Through this review, the microbial production of stilbenes is analyzed, stressing both the engineering dynamic regulation of biosynthetic pathways and the endogenous control of stilbene precursors.
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36
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Vrancheva R, Ivanov I, Aneva I, Stoyanova M, Pavlov A. Food additives and bioactive substances from in vitro systems of edible plants from the Balkan peninsula. Eng Life Sci 2018; 18:799-806. [PMID: 32624873 DOI: 10.1002/elsc.201800063] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 08/01/2018] [Accepted: 08/14/2018] [Indexed: 11/07/2022] Open
Abstract
During the last few years there is an increasing demand to the natural biologically active compounds. According to the World Health Organization (WHO) about 11% of the conventional medicines are of plant origin. Nowadays, plant biotechnologies are modern and reliable tool for producing valuable bioactive compounds. Recently, the potential of plant cells as foods also was confirmed. The advantages of plant in vitro systems over the intact plants are well known: growing under controlled and optimized laboratory conditions; independence of climatic and soil differences; preservation of rare and endangered plant species; cultivation in diverse bioreactor systems for increasing production yields of target metabolites. There have been developed many in vitro systems for production of various plant bioactive compounds with potential application in food industries. But potential for industrial implementation of this technology depends on solving problems with the scale-up of bioreactor cultivation, development of additional approaches for improving/modification of bioactivities of the target plant secondary metabolites, and to find way to exclude or replace in the culture media the carcinogenic plant growth regulator 2,4-dichlorophenoxyacetic acid (2,4-D) with its safety analogs, such as α-naphtaleneacetic acid (NAA) and/or indole-3-butyric acid (IBA). The aim of the current mini review is to summarize information about different in vitro systems of edible plants from the Balkan Peninsula with potential for producing food additives and biologically active substances and to describe prospects for successful industrial implementation of this technology.
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Affiliation(s)
- Radka Vrancheva
- Department of Analytical Chemistry and Physical chemistry University of Food Technologies-Plovdiv Plovdiv Bulgaria
| | - Ivan Ivanov
- Department of Organic Chemistry and Inorganic Chemistry University of Food Technologies-Plovdiv Plovdiv Bulgaria
| | - Ina Aneva
- Institute of Biodiversity and Ecosystem Research Bulgarian Academy of Sciences Sofia Bulgaria
| | - Magdalena Stoyanova
- Department of Analytical Chemistry and Physical chemistry University of Food Technologies-Plovdiv Plovdiv Bulgaria
| | - Atanas Pavlov
- Department of Analytical Chemistry and Physical chemistry University of Food Technologies-Plovdiv Plovdiv Bulgaria.,Laboratory of Applied Biotechnologies, The Stephan Angeloff Institute of Microbiology Bulgarian Academy of Sciences Plovdiv Bulgaria
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37
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Turner TL, Kim H, Kong II, Liu JJ, Zhang GC, Jin YS. Engineering and Evolution of Saccharomyces cerevisiae to Produce Biofuels and Chemicals. ADVANCES IN BIOCHEMICAL ENGINEERING/BIOTECHNOLOGY 2018; 162:175-215. [PMID: 27913828 DOI: 10.1007/10_2016_22] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
To mitigate global climate change caused partly by the use of fossil fuels, the production of fuels and chemicals from renewable biomass has been attempted. The conversion of various sugars from renewable biomass into biofuels by engineered baker's yeast (Saccharomyces cerevisiae) is one major direction which has grown dramatically in recent years. As well as shifting away from fossil fuels, the production of commodity chemicals by engineered S. cerevisiae has also increased significantly. The traditional approaches of biochemical and metabolic engineering to develop economic bioconversion processes in laboratory and industrial settings have been accelerated by rapid advancements in the areas of yeast genomics, synthetic biology, and systems biology. Together, these innovations have resulted in rapid and efficient manipulation of S. cerevisiae to expand fermentable substrates and diversify value-added products. Here, we discuss recent and major advances in rational (relying on prior experimentally-derived knowledge) and combinatorial (relying on high-throughput screening and genomics) approaches to engineer S. cerevisiae for producing ethanol, butanol, 2,3-butanediol, fatty acid ethyl esters, isoprenoids, organic acids, rare sugars, antioxidants, and sugar alcohols from glucose, xylose, cellobiose, galactose, acetate, alginate, mannitol, arabinose, and lactose.
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Affiliation(s)
- Timothy L Turner
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA
| | - Heejin Kim
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.,Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA
| | - In Iok Kong
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.,Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA
| | - Jing-Jing Liu
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.,Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA
| | - Guo-Chang Zhang
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA
| | - Yong-Su Jin
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. .,Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
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38
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Production of plant-derived polyphenols in microorganisms: current state and perspectives. Appl Microbiol Biotechnol 2018; 102:1575-1585. [DOI: 10.1007/s00253-018-8747-5] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 12/26/2017] [Accepted: 12/27/2017] [Indexed: 10/18/2022]
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39
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Kuo HP, Wang R, Lin YS, Lai JT, Lo YC, Huang ST. Pilot scale repeated fed-batch fermentation processes of the wine yeast Dekkera bruxellensis for mass production of resveratrol from Polygonum cuspidatum. BIORESOURCE TECHNOLOGY 2017; 243:986-993. [PMID: 28747009 DOI: 10.1016/j.biortech.2017.07.053] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Revised: 07/07/2017] [Accepted: 07/08/2017] [Indexed: 06/07/2023]
Abstract
Resveratrol has long been used as an ingredient in functional foods. Currently, Polygonum cuspidatum extract is the greatest natural source for resveratrol because of high concentrations of glycosidic-linked resveratrol. Thus, developing a cost-effective procedure to hydrolyze glucoside could substantially enhance resveratrol production from P. cuspidatum. This study selected Dekkera bruxellensis from several microorganisms based on its bioconversion and enzyme-specific activities. We demonstrated that the cells could be reused at least nine times while maintaining an average of 180.67U/L β-glucosidase activity. The average resveratrol bioconversion efficiency within five rounds of repeated usage was 108.77±0.88%. This process worked effectively when the volume was increased to 1200L, a volume at which approximately 35mgL-1h-1 resveratrol per round was produced. This repeated fed-batch bioconversion process for resveratrol production is comparable to enzyme or cell immobilization strategies in terms of reusing cycles, but without incurring additional costs for immobilization.
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Affiliation(s)
- Hsiao-Ping Kuo
- Bioresources Collection and Research Center, Food Industry Research and Development Institute, Hsinchu 30062, Taiwan
| | - Reuben Wang
- Department of Food Science, Tunghai University, Taiwan No. 1727, Sec. 4 Taiwan Boulevard, Xitun District, Taichung 40704, Taiwan
| | - Yi-Sheng Lin
- Bioresources Collection and Research Center, Food Industry Research and Development Institute, Hsinchu 30062, Taiwan
| | - Jinn-Tsyy Lai
- Bioresources Collection and Research Center, Food Industry Research and Development Institute, Hsinchu 30062, Taiwan
| | - Yi-Chen Lo
- Institute of Food Science and Technology, National Taiwan University, No. 1, Sec. 4 Roosevelt Rd., Taipei 10617, Taiwan
| | - Shyue-Tsong Huang
- Bioresources Collection and Research Center, Food Industry Research and Development Institute, Hsinchu 30062, Taiwan.
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40
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Guo H, Yang Y, Xue F, Zhang H, Huang T, Liu W, Liu H, Zhang F, Yang M, Liu C, Lu H, Zhang Y, Ma L. Effect of flexible linker length on the activity of fusion protein 4-coumaroyl-CoA ligase::stilbene synthase. MOLECULAR BIOSYSTEMS 2017; 13:598-606. [PMID: 28181620 DOI: 10.1039/c6mb00563b] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
In order to elucidate the effect of flexible linker length on the catalytic efficiency of fusion proteins, two short flexible peptide linkers of various lengths were fused between Arabidopsis thaliana 4-coumaroyl-CoA ligase (4CL) and Polygonum cuspidatum stilbene synthase (STS) to generate fusion proteins 4CL-(GSG)n-STS (n ≤ 5) and 4CL-(GGGGS)n-STS (n ≤ 4). The fusion proteins were expressed in both Escherichia coli and Saccharomyces cerevisiae, and their bioactivities were tested in vitro and in vivo using purified proteins and engineered strains, respectively. The catalytic efficiency of the fusions decreased gradually with the increase of GSG or GGGGS repeats. In both engineered S. cerevisiae and E. coli in vivo experiments, the capacity of resveratrol production decreased gradually with increasing linker length. In silico analysis showed that the prediction of homology models of fusion proteins was consistent with the in vitro and in vivo results.
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Affiliation(s)
- Huili Guo
- Key Laboratory of Urban Agriculture (North) of Ministry of Agriculture, Beijing University of Agriculture, Beijing 102206, China.
| | - Yadong Yang
- Key Laboratory of Urban Agriculture (North) of Ministry of Agriculture, Beijing University of Agriculture, Beijing 102206, China.
| | - Feiyan Xue
- Key Laboratory of Urban Agriculture (North) of Ministry of Agriculture, Beijing University of Agriculture, Beijing 102206, China.
| | - Hong Zhang
- Key Laboratory of Urban Agriculture (North) of Ministry of Agriculture, Beijing University of Agriculture, Beijing 102206, China.
| | - Tiran Huang
- Key Laboratory of Urban Agriculture (North) of Ministry of Agriculture, Beijing University of Agriculture, Beijing 102206, China.
| | - Wenbin Liu
- Key Laboratory of Urban Agriculture (North) of Ministry of Agriculture, Beijing University of Agriculture, Beijing 102206, China.
| | - Huan Liu
- Key Laboratory of Urban Agriculture (North) of Ministry of Agriculture, Beijing University of Agriculture, Beijing 102206, China.
| | - Fenqiang Zhang
- Key Laboratory of Urban Agriculture (North) of Ministry of Agriculture, Beijing University of Agriculture, Beijing 102206, China.
| | - Mingfeng Yang
- Key Laboratory of Urban Agriculture (North) of Ministry of Agriculture, Beijing University of Agriculture, Beijing 102206, China.
| | - Chunmei Liu
- Key Laboratory of Urban Agriculture (North) of Ministry of Agriculture, Beijing University of Agriculture, Beijing 102206, China.
| | - Heshu Lu
- Key Laboratory of Urban Agriculture (North) of Ministry of Agriculture, Beijing University of Agriculture, Beijing 102206, China.
| | - Yansheng Zhang
- CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, Hubei, China
| | - Lanqing Ma
- Key Laboratory of Urban Agriculture (North) of Ministry of Agriculture, Beijing University of Agriculture, Beijing 102206, China. and Beijing Collaborative Innovation Center for Eco-Environmental Improvement with Forestry and Fruit Trees, Beijing 102206, China
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41
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Chen X, Gao C, Guo L, Hu G, Luo Q, Liu J, Nielsen J, Chen J, Liu L. DCEO Biotechnology: Tools To Design, Construct, Evaluate, and Optimize the Metabolic Pathway for Biosynthesis of Chemicals. Chem Rev 2017; 118:4-72. [DOI: 10.1021/acs.chemrev.6b00804] [Citation(s) in RCA: 109] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Xiulai Chen
- State
Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- Key
Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China
| | - Cong Gao
- State
Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- Key
Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China
| | - Liang Guo
- State
Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- Key
Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China
| | - Guipeng Hu
- State
Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- Key
Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China
| | - Qiuling Luo
- State
Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- Key
Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China
| | - Jia Liu
- State
Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- Key
Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China
| | - Jens Nielsen
- Department
of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg SE-412 96, Sweden
- Novo
Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK2800 Lyngby, Denmark
| | - Jian Chen
- State
Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- Key
Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China
| | - Liming Liu
- State
Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- Department
of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg SE-412 96, Sweden
- Key
Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China
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42
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De novo biosynthesis of trans-cinnamic acid derivatives in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 2017; 101:4883-4893. [PMID: 28353001 DOI: 10.1007/s00253-017-8220-x] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Revised: 02/13/2017] [Accepted: 03/04/2017] [Indexed: 02/05/2023]
Abstract
The production of natural aroma compounds is an expanding field within the branch of white biotechnology. Three aromatic compounds of interest are cinnamaldehyde, the typical cinnamon aroma that has applications in agriculture and medical sciences, as well as cinnamyl alcohol and hydrocinnamyl alcohol, which have applications in the cosmetic industry. Current production methods, which rely on extraction from plant materials or chemical synthesis, are associated with drawbacks regarding scalability, production time, and environmental impact. These considerations make the development of a sustainable microbial-based production highly desirable. Through steps of rational metabolic engineering, we engineered the yeast Saccharomyces cerevisiae as a microbial host to produce trans-cinnamic acid derivatives cinnamaldehyde, cinnamyl alcohol, and hydrocinnamyl alcohol, from externally added trans-cinnamic acid or de novo from glucose as a carbon source. We show that the desired products can be de novo synthesized in S. cerevisiae via the heterologous overexpression of the genes encoding phenylalanine ammonia lyase 2 from Arabidopsis thaliana (AtPAL2), aryl carboxylic acid reductase (acar) from Nocardia sp., and phosphopantetheinyl transferase (entD) from Escherichia coli, together with endogenous alcohol dehydrogenases. This study provides a proof of concept and a strain that can be further optimized for production of high-value aromatic compounds.
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43
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Profiling influences of gene overexpression on heterologous resveratrol production in Saccharomyces cerevisiae. Front Chem Sci Eng 2017. [DOI: 10.1007/s11705-016-1601-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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44
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Caridi A, Sidari R, Giuffrè AM, Pellicanò TM, Sicari V, Zappia C, Poiana M. Test of four generations of Saccharomyces cerevisiae concerning their effect on antioxidant phenolic compounds in wine. Eur Food Res Technol 2017. [DOI: 10.1007/s00217-016-2840-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
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45
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Guleria S, Zhou J, Koffas MA. Nutraceuticals (Vitamin C, Carotenoids, Resveratrol). Ind Biotechnol (New Rochelle N Y) 2016. [DOI: 10.1002/9783527807833.ch10] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Affiliation(s)
- Sanjay Guleria
- Sher-e-Kashmir University of Agricultural Sciences and Technology; Division of Biochemistry, Faculty of Basic Sciences; Main Campus Chatha Jammu 180 009 India
| | - Jingwen Zhou
- Jiangnan University; Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology; 1800 Lihu Road Wuxi Jiangsu 214122 China
| | - Mattheos A.G. Koffas
- Rensselaer Polytechnic Institute; Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Center for Biotechnology and Interdisciplinary Studies; 110 8th Street Troy NY 12180 USA
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46
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Li M, Schneider K, Kristensen M, Borodina I, Nielsen J. Engineering yeast for high-level production of stilbenoid antioxidants. Sci Rep 2016; 6:36827. [PMID: 27833117 PMCID: PMC5105057 DOI: 10.1038/srep36827] [Citation(s) in RCA: 96] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Accepted: 10/21/2016] [Indexed: 01/07/2023] Open
Abstract
Stilbenoids, including resveratrol and its methylated derivatives, are natural potent antioxidants, produced by some plants in trace amounts as defense compounds. Extraction of stilbenoids from natural sources is costly due to their low abundance and often limited availability of the plant. Here we engineered the yeast Saccharomyces cerevisiae for production of stilbenoids on a simple mineral medium typically used for industrial production. We applied a pull-push-block strain engineering strategy that included overexpression of the resveratrol biosynthesis pathway, optimization of the electron transfer to the cytochrome P450 monooxygenase, increase of the precursors supply, and decrease of the pathway intermediates degradation. Fed-batch fermentation of the final strain resulted in a final titer of 800 mg l−1 resveratrol, which is by far the highest titer reported to date for production of resveratrol from glucose. We further integrated heterologous methyltransferases into the resveratrol platform strain and hereby demonstrated for the first time de novo biosynthesis of pinostilbene and pterostilbene, which have better stability and uptake in the human body, from glucose.
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Affiliation(s)
- Mingji Li
- The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK-2970 Hørsholm, Denmark
| | - Konstantin Schneider
- The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK-2970 Hørsholm, Denmark
| | - Mette Kristensen
- The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK-2970 Hørsholm, Denmark
| | - Irina Borodina
- The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK-2970 Hørsholm, Denmark
| | - Jens Nielsen
- The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK-2970 Hørsholm, Denmark.,Department of Biology and Biological Engineering, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.,The Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, SE-41296 Gothenburg, Sweden
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47
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Wong VKW, Law BYK, Yao XJ, Chen X, Xu SW, Liu L, Leung ELH. Advanced research technology for discovery of new effective compounds from Chinese herbal medicine and their molecular targets. Pharmacol Res 2016; 111:546-555. [DOI: 10.1016/j.phrs.2016.07.022] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Revised: 07/19/2016] [Accepted: 07/19/2016] [Indexed: 02/07/2023]
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48
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Pandey RP, Parajuli P, Koffas MA, Sohng JK. Microbial production of natural and non-natural flavonoids: Pathway engineering, directed evolution and systems/synthetic biology. Biotechnol Adv 2016; 34:634-662. [DOI: 10.1016/j.biotechadv.2016.02.012] [Citation(s) in RCA: 167] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2015] [Revised: 02/24/2016] [Accepted: 02/29/2016] [Indexed: 12/18/2022]
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49
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Lu Y, Shao D, Shi J, Huang Q, Yang H, Jin M. Strategies for enhancing resveratrol production and the expression of pathway enzymes. Appl Microbiol Biotechnol 2016; 100:7407-7421. [DOI: 10.1007/s00253-016-7723-1] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Revised: 06/29/2016] [Accepted: 07/01/2016] [Indexed: 01/02/2023]
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50
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Suástegui M, Shao Z. Yeast factories for the production of aromatic compounds: from building blocks to plant secondary metabolites. J Ind Microbiol Biotechnol 2016; 43:1611-1624. [PMID: 27581441 DOI: 10.1007/s10295-016-1824-9] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Accepted: 08/02/2016] [Indexed: 12/23/2022]
Abstract
The aromatic amino acid biosynthesis pathway is a source to a plethora of commercially relevant chemicals with very diverse industrial applications. Tremendous efforts in microbial engineering have led to the production of compounds ranging from small aromatic molecular building blocks all the way to intricate plant secondary metabolites. Particularly, the yeast Saccharomyces cerevisiae has been a great model organism given its superior capability to heterologously express long metabolic pathways, especially the ones containing cytochrome P450 enzymes. This review contains a collection of state-of-the-art metabolic engineering work devoted towards unraveling the mechanisms for enhancing the flux of carbon into the aromatic pathway. Some of the molecules discussed include the polymer precursor muconic acid, as well as important nutraceuticals (flavonoids and stilbenoids), and opium-derived drugs (benzylisoquinoline alkaloids).
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Affiliation(s)
- Miguel Suástegui
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, 50010, USA.,NSF Engineering Research Center for Biorenewable Chemicals, Iowa State University, Ames, IA, 50010, USA
| | - Zengyi Shao
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, 50010, USA. .,Microbiology Interdisciplinary Program, Iowa State University, Ames, IA, 50010, USA. .,NSF Engineering Research Center for Biorenewable Chemicals, Iowa State University, Ames, IA, 50010, USA.
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