Please wait a minute...

中国生物工程杂志

China Biotechnology
China Biotechnology  2016, Vol. 36 Issue (11): 83-89    DOI: 10.13523/j.cb.20161112
    
Progress and Prospect of Heterologous Biosynthesis of Ttriterpenoids in Engineered Escherichia coli
ZHANG Qiang, LI Da shuai, LU Wen yu
Department of Biological Engineering, School of Chemical Engineering and Technology, Tianjin University, Key Laboratory of Systems Bioengineering, Ministry of Education, SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China
Download:   PDF(582KB) HTML
Export: BibTeX | EndNote (RIS)      

Abstract  

Triterpenoids are the major pharmacologically active constituents of many medicinal plants, which exhibit potential economic value. Currently, triterpenoids are mainly produced through their extraction from plants which is complicated, time-consuming, labour intensive and produce relatively low yields. Escherichia coli as a commonly used recombinant microbial system has the ability to generate valuable natural products, so, heterologous biosynthesis of triterpenoids or precursors in E. coli presents an attractive system. Research progress of heterologous biosynthesis of triterpenoids is summarized, including metabolic pathway, key enzymes and optimization of E. coli chassis and introduction of functional modules. Basic problems on efficient synthesis of triterpenoids in E. coli are discussed and a prospect of using E. coli as a new chassis of biosynthesis of triterpenoids is analyzed.



Key wordsSynthetic biology      Heterologous biosynthesis      Escherichia coli      Triterpenoids     
Received: 21 April 2016      Published: 25 November 2016
ZTFLH:  Q93-91  
Cite this article:

ZHANG Qiang, LI Da shuai, LU Wen yu. Progress and Prospect of Heterologous Biosynthesis of Ttriterpenoids in Engineered Escherichia coli. China Biotechnology, 2016, 36(11): 83-89.

URL:

http://manu60.magtech.com.cn/biotech/10.13523/j.cb.20161112     OR     http://manu60.magtech.com.cn/biotech/Y2016/V36/I11/83

[1] Phillips D R, Rasbery J M, Bartel B, et al. Biosynthetic diversity in plant triterpene cyclization. Current Opinion in Plant Biology, 2006, 9(3):305-314.
[2] Watanabe K. Proceedings:effective use of heterologous hosts for characterization of biosynthetic enzymes allows production of natural products and promotes new natural product discovery. The Japanese journal of antibiotics, 2015, 68(1):55-67.
[3] Thimmappa R, Geisler K, Louveau T, et al. Triterpene biosynthesis in plants. Annual Review of Plant Biology, 2014, 65(1):225-257.
[4] Hoshino T,Sato T.Squalene-hopene cyclase:catalytic mechanism and substrate recognition. Chemical Communications, 2002,33(4):291-301.
[5] Augustin J M, Kuzina V, Andersen S B, et al. Molecular activities, biosynthesis and evolution of triterpenoid saponins. Phytochemistry, 2011, 72(6):435-457.
[6] Facchini P J, Bohlmann J, Covello P S, et al. Synthetic biosystems for the production of high-value plant metabolites. Trends in Biotechnology, 2012, 30(3):127-131.
[7] Thimmappa R, Geisler K, Louveau T, et al. Triterpene biosynthesis in plants. Annual Review of Plant Biology, 2014, 65(1):225-257.
[8] Dai Z, Liu Y, Zhang X, et al. Metabolic engineering of Saccharomyces cerevisiae for production of ginsenosides. Metabolic Engineering, 2013, 20(5):146-156.
[9] Dai Z, Wang B, Liu Y, et al. Producing aglycons of ginsenosides in bakers' yeast. Scientific Reports, 2014, 4(4):3698.
[10] Zhao F, Bai P, Liu T, et al. Optimization of a cytochrome P450 oxidation system for enhancing protopanaxadiol production in Saccharomyces cerevisiae. Biotechnology and Bioengineering, 2016,113(8):1787-1795.
[11] Yan X, Fan Y, Wei W, et al. Production of bioactive ginsenoside compound K in metabolically engineered yeast. Cell Research, 2014, 24(6):770-773.
[12] Wang P, Wei Y, Fan Y, et al. Production of bioactive ginsenosides Rh2 and Rg3 by metabolically engineered yeasts. Metabolic Engineering, 2015, 29:97-105.
[13] Moses T, Pollier J, Almagro L, et al. Combinatorial biosynthesis of sapogenins and saponins in Saccharomyces cerevisiae using a C-16α hydroxylase from Bupleurum falcatum. Proceedings of the National Academy of Sciences, 2014, 111(4):1634-1639.
[14] Davidovich-Rikanati R, Shalev L, Baranes N, et al. Recombinant yeast as a functional tool for understanding bitterness and cucurbitacin biosynthesis in watermelon (Citrullus spp.). Yeast, 2015, 32(1):103-114.
[15] Huang L, Li J, Ye H, et al. Molecular characterization of the pentacyclic triterpenoid biosynthetic pathway in Catharanthus roseus. Planta, 2012, 236(5):1571-1581.
[16] Li D, Zhang Q, Zhou Z, et al. Heterologous biosynthesis of triterpenoid dammarenediol-Ⅱ in engineered Escherichia coli. Biotechnology Letters, 2016, 38(4):1-7.
[17] Katabami A, Li L, Iwasaki M, et al. Production of squalene by squalene synthases and their truncated mutants in Escherichia coli. Journal of Bioscience and Bioengineering, 2015, 119(2):165-171.
[18] Laden B P, Tang Y,Porter T D. Cloning, heterologous expression, and enzymological characterization of human squalene monooxygenase. Archives of Biochemistry and Biophysics, 2000, 374(2):381-388.
[19] Jiang M, Stephanopoulos G, Pfeifer B A. Toward biosynthetic design and implementation of Escherichia coli-derived paclitaxel and other heterologous polyisoprene compounds. Applied and Environmental Microbiology, 2012, 78(8):2497-2504.
[20] Leonard E,Koffas M G.Engineering of artificial plant cytochrome P450 enzymes for synthesis of iIsoflavones by Escherichia coli. Applied and Environmental Microbiology, 2007, 73(22):7246-7251.
[21] Ajikumar P K, Xiao W H, Tyo K E, et al. Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli. Science, 2010, 330(6000):70-74.
[22] Tsuruta H, Paddon C J, Eng D, et al. High-level production of amorpha-4, 11-diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli. PLoS One, 2009, 4(2):e4489.
[23] Tansakul P, Shibuya M, Kushiro T, et al. Dammarenediol-Ⅱ synthase, the first dedicated enzyme for ginsenoside biosynthesis, in Panax ginseng. FEBS Letters, 2006, 580(22):5143-5149.
[24] Li J,Zhang Y.Increase of betulinic acid production in Saccharomyces cerevisiae by balancing fatty acids and betulinic acid forming pathways. Applied Microbiology and Biotechnology, 2014, 98(7):3081-3089.
[25] Fukushima E O, Seki H, Ohyama K, et al. CYP716A subfamily members are multifunctional oxidases in triterpenoid biosynthesis. Plant and Cell Physiology, 2011, 52(12):2050-2061.
[26] Shibuya M, Zhang H, Endo A, et al. Two branches of the lupeol synthase gene in the molecular evolution of plant oxidosqualene cyclases. European Journal of Biochemistry, 1999, 266(1):302-307.
[27] Castillo D A, Kolesnikova M D, Matsuda S P. An effective strategy for exploring unknown metabolic pathways by genome mining. Journal of the American Chemical Society, 2013, 135(15):5885-5894.
[28] Field B, Fiston-Lavier AS, Kemen A, et al. Formation of plant metabolic gene clusters within dynamic chromosomal regions. Proceedings of the National Academy of Sciences, 2011, 108(38):16116-16121.
[29] Fukushima E O, Seki H, Ohyama K, et al. CYP716A subfamily members are multifunctional oxidases in triterpenoid biosynthesis. Plant and Cell Physiology, 2011, 52(12):2050-2061.
[30] Ba L, Li P, Zhang H, et al. Semi-rational engineering of cytochrome P450sca-2 in a hybrid system for enhanced catalytic activity:Insights into the important role of electron transfer. Biotechnology and Bioengineering, 2013, 110(11):2815-2825.
[31] Fasan R, Crook N C, Peters M W, et al. Improved product-per-glucose yields in P450-dependent propane biotransformations using engineered Escherichia coli. Biotechnology and Bioengineering, 2011, 108(3):500-510.
[32] Li S, Podust L M,Sherman D H.Engineering and analysis of a self-sufficient biosynthetic cytochrome P450 PikC fused to the RhFRED reductase domain. Journal of the American Chemical Society, 2007, 129(43):12940-12941.
[33] Shen A L, Porter T, Wilson T, et al. Structural analysis of the FMN binding domain of NADPH-cytochrome P-450 oxidoreductase by site-directed mutagenesis. Journal of Biological Chemistry, 1989, 264(13):7584-7589.
[34] Venkateswarlu K, Lamb D C, Kelly D E, et al. The N-terminal membrane domain of yeast NADPH-cytochrome P450(CYP) oxidoreductase is not required for catalytic activity in sterol biosynthesis or in reconstitution of CYP activity. Journal of Biological Chemistry, 1998, 273(8):4492-4496.
[35] Sadeghi S J,Gilardi G.Chimeric P450 enzymes:activity of artificial redox fusions driven by different reductases for biotechnological applications. Biotechnology and Applied Biochemistry, 2013, 60(1):102-110.
[36] Meesapyodsuk D, Balsevich J, Reed D W, et al. Saponin biosynthesis in Saponaria vaccaria cDNAs encoding β-amyrin synthase and a triterpene carboxylic acid glucosyltransferase. Plant Physiology, 2007, 143(2):959-969.
[37] Naoumkina M A, Modolo L V, Huhman D V, et al. Genomic and coexpression analyses predict multiple genes involved in triterpene saponin biosynthesis in Medicago truncatula. The Plant Cell, 2010, 22(3):850-866.
[38] Wang J, Li S, Xiong Z, et al. Pathway mining-based integration of critical enzyme parts for de novo biosynthesis of steviolglycosides sweetener in Escherichia coli. Cell Research, 2015,26(2):1-4.
[39] Peralta-Yahya P P, Ouellet M, Chan R, et al. Identification and microbial production of a terpene-based advanced biofuel. Nature Communications, 2011, 2(9):2749-2763.
[40] Sliva A, Yang H, Boeke J D, et al. Freedom and responsibility in synthetic genomics:The Synthetic yeast project. Genetics, 2015, 200(4):1021-1028.

[1] ZHANG Wei, LIU Duo, LI Bing-zhi, YUAN Ying-jin. Construction and Optimization of p-coumaric Acid Producing Saccharomyces cerevisiae[J]. China Biotechnology, 2017, 37(9): 89-97.
[2] LI Bo, LIANG Nan, LIU Duo, LIU Hong, WANG Ying, XIAO Wen-hai, YAO Ming-dong, YUAN Ying-jin. Metabolic Engineering of Saccharomyces cerevisiae for Production of 8-Dimenthylally Naringenin[J]. China Biotechnology, 2017, 37(9): 71-81.
[3] WEN Guo-xia, HUANG Zi-hao, TAN Jun-jie, KAN Nai-peng, LING Jing-yi, ZHANG Xia, LIU Gang, CHEN Hui-peng. Construction of XylR-Pugene Lines in Escherichia coli to Detect 2,4,6-trinitrotoluene[J]. China Biotechnology, 2017, 37(7): 105-114.
[4] ZHANG Yue-ming, QIAO Jian-jun. Mechanism of Acid Tolerance in Acidophiles with pH Homeostasis and Its Potential Applications[J]. China Biotechnology, 2017, 37(12): 103-110.
[5] HU Li-qiang, ZHENG Wen, ZHONG Yi, DU Dan, YANG Hao, GONG Meng. Comparison of Expression and Activity of Antiviral Protein RC28 in Escherichia coli and Pichia pastoris[J]. China Biotechnology, 2017, 37(1): 14-20.
[6] MEI Xue-ang, CHEN Yan, WANG Rui-zhao, XIAO Wen-hai, WANG Ying, LI Xia, YUAN Ying-jin. Engineered Yeast Cell for Producing Zeaxanthin[J]. China Biotechnology, 2016, 36(8): 64-72.
[7] LI Xiao-bo, LIU Xue, ZHAO Guang-rong. Advances on Flavonoid Glycosides Production of Engineered Microorganisms[J]. China Biotechnology, 2016, 36(8): 105-112.
[8] CHEN Da-Ming, LIU Xiao, MAO Kai-Yun, XIONG Yan. Development Status and Trend Analysis of Synthetic Biology Products[J]. China Biotechnology, 2016, 36(7): 117-126.
[9] WANG Rui-zhao, PAN Cai-hui, WANG Ying, XIAO Wen-hai, YUAN Ying-jin. Design and Construction of highβ-carotene Producing Saccharomyces cerevisiae[J]. China Biotechnology, 2016, 36(7): 83-91.
[10] ZHANG Wen-qian, XIAO Wen-hai, ZHOU Xiao, WANG Ying. Effect of Post-squalene Genes on the Synthesis of 7-Dehydrocholesterol in the Artificial Saccharomyces cerevisiae[J]. China Biotechnology, 2016, 36(6): 39-50.
[11] LIU Bao-li, LIU Gao-gang, LIN Qiu-hui, LI Bing-zhi, YUAN Ying-jin. Construction of Recombinant Xylose-utilizing Saccharomyces cerevisiae by Three-plasmid Co-transformation Combinatorial Screening Method[J]. China Biotechnology, 2016, 36(12): 86-97.
[12] WU Xue-long, YANG Xiao-hui, WANG Jun-qing, WANG Rui-ming. Expression and Characteristics of Apis mellifera NADPH-cytochrome P450 Reductase Gene in Escherichia coli[J]. China Biotechnology, 2016, 36(12): 28-35.
[13] FANG Li xia, CAO Ying xiu, SONG Hao. Engineering Escherichia coli to Synthesize Free Fatty Acids: A Recent Progress[J]. China Biotechnology, 2016, 36(11): 90-97.
[14] XIONG Yuan-yuan, LU Chuan-dong, TAO Ye, ZHAO Jin-fang. Fermentative Production of L-lactic Acid from Wastepaper by Recombinant Escherichia coli WL204[J]. China Biotechnology, 2015, 35(5): 49-54.
[15] GUO Zhao-lai, BAI Xue-gui, YAN Jin-ping, CHEN Xuan-qin, LI Kun-zhi, XU Hui-ni. Prokaryotic Expression and Function Analysis of SoHb from Spinach[J]. China Biotechnology, 2015, 35(4): 54-59.