Please wait a minute...

中国生物工程杂志

China Biotechnology
China Biotechnology  2014, Vol. 34 Issue (4): 110-117    DOI: 10.13523/j.cb.20140417
    
Advances on Flavonoids Production of Engineered Microorganisms
ZHAO Ying, LIU Jin, WANG Chang-song, ZHAO Guang-rong
Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin University, Tianjin 300072, China
Download: HTML   PDF(1019KB) HTML
Export: BibTeX | EndNote (RIS)      

Abstract  

Flavonoids, plant-specific polyphenolic compounds, have significant physiological activities, including antioxidant, anti-inflammatory effects, and improvement of blood circulation. They have promising markets for health products, cosmetics and medicines. At present, flavonoids are mainly extracted from plants, but their growth are restricted by the seasons, location and varieties, their separation and purification processes are complex and low efficiency. With the development of synthetic biology and metabolic engineering, the flavonoids metabolic circuits have been constructed, optimization and combination of gene sequences from different sources and chassis modification have been achieved. Now engineered yeast, Escherichia coli and other microorganisms have been able to produce 2s-flavanones, flavones, isoflavonoids, flavonols, anthocyanins and flavanones which can be modified to creat new products with noval biological activities by methylase or glycosylase. The research achievement on flavonoids production in engineered microorganisms was reviewed and the future trend of development was explored.



Key wordsFlavonoids      Microbial Synthesis      Synthetic biology      Recombinant microorganism     
Received: 18 February 2014      Published: 25 April 2014
ZTFLH:  Q819  
Cite this article:

ZHAO Ying, LIU Jin, WANG Chang-song, ZHAO Guang-rong. Advances on Flavonoids Production of Engineered Microorganisms. China Biotechnology, 2014, 34(4): 110-117.

URL:

https://manu60.magtech.com.cn/biotech/10.13523/j.cb.20140417     OR     https://manu60.magtech.com.cn/biotech/Y2014/V34/I4/110


[1] Yao L H, Jiang Y M, Shi J, et al. Flavonoids in food and their health benefits. Plant Foods for Human Nutrition, 2004,59(3):113-122.

[2] Middleton E, Kandaswami C, Theoharides T C. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacological Reviews, 2000,52(4):673-751.

[3] Rice-Evans C A, Miller N J, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radical Biology & Medicine, 1996,20(7):933-956.

[4] Mavel S, Dikic B, Palakas S, et al. Synthesis and biological evaluation of a series of flavone derivatives as potential radioligands for imaging the multidrug resistance-associated protein 1 (ABCC1/MRP1). Bioorganic & Medicinal Chemistry, 2006,14(5):1599-1607.

[5] Winkel-Shirley B. Flavonoid biosynthesis. A colorful model for genetics, biochemistry, cell biology, and biotechnology. Plant Physiology, 2001,126(2):485-493.

[6] Hwang E I, Kaneko M, Ohnishi Y, et al. Production of plant-specific flavanones by Escherichia coli containing an artificial gene cluster. Applied and Environmental Microbiology, 2003,69(5):2699-2706.

[7] Santos C N, Koffas M, Stephanopoulos G. Optimization of a heterologous pathway for the production of flavonoids from glucose. Metabolic Engineering, 2011,13(4):392-400.

[8] Jiang H, Morgan J A. Optimization of an in vivo plant P450 monooxygenase system in Saccharomyces cerevisiae. Biotechnology and Bioengineering, 2004,85(2):130-137.

[9] Yan Y, Kohli A, Koffas M A. Biosynthesis of natural flavanones in Saccharomyces cerevisiae. Applied and Environmental Microbiology, 2005,71(9):5610-5613.

[10] Koopman F, Beekwilder J, Crimi B, et al. De novo production of the flavonoid naringenin in engineered Saccharomyces cerevisiae. Microbial Cell Factories, 2012,11:155.

[11] Takamura Y, Nomura G. Changes in the intracellular concentration of acetyl-CoA and malonyl-CoA in relation to the carbon and energy metabolism of Escherichia coli K12. Journal of General Microbiology, 1988,134(8):2249-2253.

[12] Miyahisa I, Kaneko M, Funa N, et al. Efficient production of (2S)-flavanones by Escherichia coli containing an artificial biosynthetic gene cluster. Applied Microbiology and Biotechnology, 2005,68(4):498-504.

[13] Leonard E, Lim K H, Saw P N, et al. Engineering central metabolic pathways for high-level flavonoid production in Escherichia coli. Applied and Environmental Microbiology, 2007,73(12):3877-3886.

[14] Burgard A P, Pharkya P, Maranas C D. Optknock: a bilevel programming framework for identifying gene knockout strategies for microbial strain optimization. Biotechnology and Bioengineering, 2003,84(6):647-657.

[15] Tepper N, Shlomi T. Predicting metabolic engineering knockout strategies for chemical production: accounting for competing pathways. Bioinformatics, 2010,26(4):536-543.

[16] Fowler Z L, Gikandi W W, Koffas M A. Increased malonyl coenzyme A biosynthesis by tuning the Escherichia coli metabolic network and its application to flavanone production. Applied and Environmental Microbiology, 2009,75(18):5831-5839.

[17] Xu P, Ranganathan S, Fowler Z L, et al. Genome-scale metabolic network modeling results in minimal interventions that cooperatively force carbon flux towards malonyl-CoA. Metabolic Engineering, 2011,13(5):578-587.

[18] Zhu S, Wu J, Du G, et al. Efficient synthesis of eriodictyol from L-tyrosine in Escherichia coli. Applied and Environmental Microbiology, 2014, doi:10.1128/AEM. 03986-13.

[19] Wu J, Du G, Zhou J, et al. Metabolic engineering of Escherichia coli for (2S)-pinocembrin production from glucose by a modular metabolic strategy. Metabolic Engineering, 2013,16:48-55.

[20] Leonard E, Chemler J, Lim K H, et al. Expression of a soluble flavone synthase allows the biosynthesis of phytoestrogen derivatives in Escherichia coli. Applied Microbiology and Biotechnology, 2006,70(1):85-91.

[21] Fotsis T, Pepper M, Adlercreutz H, et al. Genistein, a dietary ingested isoflavonoid, inhibits cell proliferation and in vitro angiogenesis. The Journal of Nutrition, 1995,125(3 Suppl):790S-797S.

[22] 陈尚武,郝佳, 马会勤. 大豆异黄酮代谢途径在大肠杆菌中的构建及表达. 生物工程学报, 2007,23(6):1022-1028. Chen S W, Hao J, Ma H Q. Construction and expression of the soybean isoflavonoid biosynthetic pathway in Escherichia coli. Chinese Journal of Biotechnology, 2007,23(6):1022-1028.

[23] Sevrioukova I F, Li H, Zhang H, et al. Structure of a cytochrome P450-redox partner electron-transfer complex. Proceedings of the National Academy of Sciences of the United States of America, 1999,96(5):1863-1868.

[24] Barnes H J, Arlotto M P, Waterman M R. Expression and enzymatic activity of recombinant cytochrome P450 17 alpha-hydroxylase in Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America, 1991,88(13):5597-5601.

[25] Katsuyama Y, Miyahisa I, Funa N, et al. One-pot synthesis of genistein from tyrosine by coincubation of genetically engineered Escherichia coli and Saccharomyces cerevisiae cells. Applied Microbiology and Biotechnology, 2007,73(5):1143-1149.

[26] Trantas E, Panopoulos N, Ververidis F. Metabolic engineering of the complete pathway leading to heterologous biosynthesis of various flavonoids and stilbenoids in Saccharomyces cerevisiae. Metabolic Engineering, 2009,11(6):355-366.

[27] Leonard E, Koffas M A. Engineering of artificial plant cytochrome P450 enzymes for synthesis of isoflavones by Escherichia coli. Applied and Environmental Microbiology, 2007,73(22):7246-7251.

[28] Formica J V, Regelson W. Review of the biology of quercetin and related bioflavonoids. Food and Chemical Toxicology, 1995,33(12):1061-1080.

[29] Lamson D W, Brignall M S. Antioxidants and cancer, part 3: quercetin. Journal of Clinical Therapeutic, 2000,5(3):196-208.

[30] Leonard E, Yan Y, Koffas M A. Functional expression of a P450 flavonoid hydroxylase for the biosynthesis of plant-specific hydroxylated flavonols in Escherichia coli. Metabolic Engineering, 2006,8(2):172-181.

[31] Kahkonen M P, Heinonen M. Antioxidant activity of anthocyanins and their aglycons. Journal of Agricultural and Food Chemistry, 2003,51(3):628-633.

[32] Noda Y, Kneyuki T, Igarashi K, et al. Antioxidant activity of nasunin, an anthocyanin in eggplant peels. Toxicology, 2000,148(2-3):119-123.

[33] Yan Y, Chemler J, Huang L, et al. Metabolic engineering of anthocyanin biosynthesis in Escherichia coli. Applied and Environmental Microbiology, 2005,71(7):3617-3623.

[34] Yan Y, Li Z, Koffas M A. High-yield anthocyanin biosynthesis in engineered Escherichia coli. Biotechnology and Bioengineering, 2008,100(1):126-140.

[35] Higdon J V, Frei B. Tea catechins and polyphenols: health effects, metabolism, and antioxidant functions. Critical Reviews in Food Science and Nutrition, 2003,43(1):89-143.

[36] Muramatsu K, Fukuyo M, Hara Y. Effect of green tea catechins on plasma cholesterol level in cholesterol-fed rats. Journal of Nutritional Science and Vitaminology, 1986,32(6):613-622.

[37] Nagao T, Meguro S, Hase T, et al. A catechin-rich beverage improves obesity and blood glucose control in patients with type 2 diabetes. Obesity, 2009,17(2):310-317.

[38] Chemler J A, Lock L T, Koffas M A, et al. Standardized biosynthesis of flavan-3-ols with effects on pancreatic beta-cell insulin secretion. Applied Microbiology and Biotechnology, 2007,77(4):797-807.

[39] Kim H, Park B S, Lee K G, et al. Effects of naturally occurring compounds on fibril formation and oxidative stress of beta-amyloid. Journal of Agricultural and Food Chemistry, 2005,53(22):8537-8541.

[40] Bao M, Lou Y. Isorhamnetin prevent endothelial cell injuries from oxidized LDL via activation of p38MAPK. European Journal of Pharmacology, 2006,547(1-3):22-30.

[41] Castrillo J L, Carrasco L. Action of 3-methylquercetin on poliovirus RNA replication. Journal of Virology, 1987,61(10):3319-3321.

[42] Kim M J, Kim B G, Ahn J H. Biosynthesis of bioactive O-methylated flavonoids in Escherichia coli. Applied Microbiology and Biotechnology, 2013,97(16):7195-7204.

[43] Zhang W Y, Lee J J, Kim I S, et al. 7-O-methylaromadendrin stimulates glucose uptake and improves insulin resistance in vitro. Biological & Pharmaceutical Bulletin, 2010,33(9):1494-1499.

[44] Malla S, Koffas M A, Kazlauskas R J, et al. Production of 7-O-methyl aromadendrin, a medicinally valuable flavonoid, in Escherichia coli. Applied and Environmental Microbiology, 2012,78(3):684-694.

[45] Kramer C M, Prata R T, Willits M G, et al. Cloning and regiospecificity studies of two flavonoid glucosyltransferases from Allium cepa. Phytochemistry, 2003,64(6):1069-1076.

[46] Thuan N H, Park J W, Sohng J K. Toward the production of flavone-7-O-β-d-glucopyranosides using Arabidopsis glycosyltransferase in Escherichia coli. Process Biochemistry,2013,48(11):1744-1748.

[47] Soundararajan R, Wishart A D, Rupasinghe H P, et al. Quercetin 3-glucoside protects neuroblastoma (SH-SY5Y) cells in vitro against oxidative damage by inducing sterol regulatory element-binding protein-2-mediated cholesterol biosynthesis. The Journal of Biological Chemistry, 2008,283(4):2231-2245.

[48] Juergenliemk G, Boje K, Huewel S, et al. In vitro studies indicate that miquelianin (quercetin 3-O-beta-D-glucuronopyranoside) is able to reach the CNS from the small intestine. Planta Medica, 2003,69(11):1013-1017.

[49] Yoon J A, Kim B G, Lee W J, et al. Production of a novel quercetin glycoside through metabolic engineering of Escherichia coli. Applied and Environmental Microbiology, 2012,78(12):4256-4262.

[50] Walsh C T. Combinatorial biosynthesis of antibiotics: challenges and opportunities. Chembiochem, 2002,3(2-3):125-134.

[51] Katsuyama Y, Funa N, Miyahisa I, et al. Synthesis of unnatural flavonoids and stilbenes by exploiting the plant biosynthetic pathway in Escherichia coli. Chemistry & Biology, 2007,14(6):613-621.

[52] Chemler J A, Yan Y, Leonard E, et al. Combinatorial mutasynthesis of flavonoid analogues from acrylic acids in microorganisms. Organic Letters, 2007,9(10):1855-1858.

[1] MA Ning,WANG Han-jie. Advances of Optogenetics in the Regulation of Bacterial Production[J]. China Biotechnology, 2021, 41(9): 101-109.
[2] HUANG Huan-bang,WU Yang,YANG You-hui,WANG Zhao-guan,QI Hao. Progress in Incorporation of Non-canonical Amino Acid Based on Archaeal Tyrosyl-tRNA Synthetase[J]. China Biotechnology, 2021, 41(9): 110-125.
[3] GUO Man-man,TIAN Kai-ren,QIAO Jian-jun,LI Yan-ni. Application of Phage Recombinase Systems in Synthetic Biology[J]. China Biotechnology, 2021, 41(8): 90-102.
[4] DONG Shu-xin,QIN Lei,LI Chun,LI Jun. Transcription Factor Engineering Harnesses Metabolic Networks to Meet Efficient Production in Cell Factories[J]. China Biotechnology, 2021, 41(4): 55-63.
[5] ZHENG Yi,GUO Shi-ying,SUI Feng-xiang,YANG Qi-yu,WEI Ya-xuan,LI Xiao-yan. Applications of Quorum Sensing Systems in Synthetic Biology[J]. China Biotechnology, 2021, 41(11): 100-109.
[6] CHA Ya-ping, ZHU Mu-zi, LI Shuang. Research Progress on In Vivo Continuous Directed Evolution[J]. China Biotechnology, 2021, 41(1): 42-51.
[7] GUO Er-peng, ZHANG Jian-zhi, SI Tong. Recent Advances in the High-throughput Engineering of Lanthipeptides[J]. China Biotechnology, 2021, 41(1): 30-41.
[8] CHANG Lu, HUANG Jiao-fang, DONG Hao, ZHOU Bin-hui, ZHU Xiao-juan, ZHUANG Ying-ping. A Review on Bioremediation and Detection of Heavy Metal Pollution by Synthetic Biological Engineered Microorganisms and Biofilms[J]. China Biotechnology, 2021, 41(1): 62-71.
[9] RAO Hai-mi,LIANG Dong-mei,LI Wei-guo,QIAO Jian-jun,CAI YIN Qing-ge-le. Advances in Synthetic Biology of Fungal Aromatic Polyketides[J]. China Biotechnology, 2020, 40(9): 52-61.
[10] ZHANG Yu-ting,LI Wei-guo,LIANG Dong-mei,QIAO Jian-jun,CAI YIN Qing-ge-le. Research Progress in Synthetic Biology of P450s in Terpenoid Synthesis[J]. China Biotechnology, 2020, 40(8): 84-96.
[11] WANG Zhen,LI Xia,YUAN Ying-jin. Advances in Production of Caffeic Acid and Its Ester Derivatives in Heterologous Microbes[J]. China Biotechnology, 2020, 40(7): 91-99.
[12] SUN Qing,LIU De-hua,CHEN Zhen. Research Progress of Methanol Utilization and Bioconversion[J]. China Biotechnology, 2020, 40(10): 65-75.
[13] LIU Jin-cong,LIU Xue,YU Hong-jian,ZHAO Guang-rong. Recent Advances in Microbial Production of Phloretin and Its Glycosides[J]. China Biotechnology, 2020, 40(10): 76-84.
[14] Hua-ling XIE,Dong-qiao LI,Pei-juan CHI,Yan-ping YANG. An Analysis on the Competition of Patents in Synthetic Biology[J]. China Biotechnology, 2019, 39(4): 114-123.
[15] Si-li YU,Xue LIU,Zhao-yu ZHANG,Hong-jian YU,Guang-rong ZHAO. Advances of Betalains Biosynthesis and Metabolic Regulation[J]. China Biotechnology, 2018, 38(8): 84-91.