人参皂苷化合物生物合成进展 <sup>*</sup>

doi:10.13523/j.cb.2010014

中国生物工程杂志

2021, Vol. 41

Issue (1): 80-93 DOI: 10.13523/j.cb.2010014

综述

人参皂苷化合物生物合成进展 ^*

刘啸尘^1,²,范代娣^1,²,杨帆¹,武占省^1,^**(

)

1 西安工程大学环境与化学工程学院西安市纺织化工助剂重点实验室西安 710048
2 西北大学化工学院陕西省生物材料与发酵工程技术研究中心西安 710069

Advances in Microbial Production of Ginsenoside and Its Derivatives

LIU Xiao-chen^1,²,FAN Dai-di^1,²,YANG Fan¹,WU Zhan-sheng^1,^**(

)

1 Xian Key Laboratory of Textile Chemical Engineering Auxiliaries, School of Environmental and Chemical Engineering, Xi’an Polytechnic University, Xi’an 710048, China
2 Shaanxi R&D Center of Biomaterials and Fermentation Engineering, College of Chemical Engineering, Northwest University, Xi’an 710069, China

全文: PDF(4854 KB) HTML

摘要：

人参皂苷是我国许多传统名贵药用植物的主要活性物质,在医药、保健品、营养品和化妆品开发领域有广阔的应用前景,特别是稀有人参皂苷具有显著的抗肿瘤、保护神经系统、保肝护肝等药理活性。但其在植物中含量低且不稳定,严重影响了人参皂苷类物质的开发利用。自20世纪末以来,随着生物技术的不断发展和多种生物基因组的测序和解析,使得人参皂苷通过异源细胞的生物合成来解决以上问题成为可能。因此,如何构建人参皂苷人工合成体系、调控人参皂苷生物合成及提高皂苷产量引起了越来越多的关注。综述了人参皂苷的异源人工合成途径的构建及其生物合成调控方面的研究进展,并针对人参皂苷生物合成及调控过程中存在的问题以及未来的研究方向进行了总结和展望。

关键词： 人参皂苷; 生物合成; 基因挖掘; 底盘细胞; 调控策略

Abstract:

Ginsenosides are the main active substances of traditional medicinal plants and are widely used in the fields of medicine, health care products, nutritional products and cosmetics. In particular, rare ginsenosides have a variety of biological activities, such as significant anti-tumor activity and nervous system protection and liver protection function. However, the low yield of rare ginsenosides in plants seriously affects its development and utilization. Since the end of the 20th century, with the continuous development of biotechnology and genome sequencing, the problem of low production of ginsenosides can be solved by heterologous synthesis of ginsenosides in microorganisms. Therefore, it has attracted more and more attentions such as constructing an artificial synthetic system of ginsenosides, regulating ginsenoside biosynthesis strategies, and increasing the yield of saponinsin microorganisms. We reviewed the construction of heterologous synthetic pathways of ginsenosides and the research progress of their biosynthetic regulation strategies in this review. Finally, we summarized and prospected the future research directions of ginsenosides synthesis process and regulation process in microorganisms.

Key words: Ginsenosides Biosynthesis Gene mining Chassis cells Regulatory strategies

收稿日期: 2020-10-15 出版日期: 2021-02-09

ZTFLH:

Q819

基金资助: * 国家自然科学基金(22008186);陕西省自然科学基础研究计划(2019JQ-523)

通讯作者: 武占省 E-mail: wuzhans@126.com

	服务
	把本文推荐给朋友
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	刘啸尘
	范代娣
	杨帆
	武占省

引用本文:

刘啸尘, 范代娣, 杨帆, 武占省. 人参皂苷化合物生物合成进展 ^*[J]. 中国生物工程杂志, 2021, 41(1): 80-93.

LIU Xiao-chen, FAN Dai-di, YANG Fan, WU Zhan-sheng. Advances in Microbial Production of Ginsenoside and Its Derivatives. China Biotechnology, 2021, 41(1): 80-93.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2010014 或 https://manu60.magtech.com.cn/biotech/CN/Y2021/V41/I1/80

图1 不同类型的人参皂苷化合物

图2 人参皂苷化合物生物合成途径

表1 人参皂苷生物合成过程中代谢中间产物及其结构

表2 人参皂苷生物合成过程的酶及其功能

表3 人参皂苷生物合成过程中关键酶基因挖掘

图3 底盘细胞优化[76]

[1]	Christensen L P. Ginsenosides: chemistry, biosynthesis, analysis, and potential health effects. Advances in Food and Nutrition Research, 2009,55:1-99. doi: 10.1016/S1043-4526(08)00401-4 pmid: 18772102
[2]	吴琼, 周应群, 孙超, 等. 人参皂苷生物合成和次生代谢工程. 中国生物工程杂志, 2009,29(10):102-108.
	Wu Q, Zhou Y Q, Sun C, et al. Progress in ginsenosides biosynthesis and prospect of the secondary metabolic engineering for the production of ginsenosides. China Biotechnology, 2009,29(10):102-108.
[3]	Murthy H N, Georgiev M I, Kim Y S, et al. Ginsenosides: prospective for sustainable biotechnological production. Applied Microbiology and Biotechnology. 2014,98(14):6243-6254.
[4]	于丽莉, 张美萍, 王康宇, 等. 人参皂苷生物合成调控的研究进展. 吉林农业. 2014(5):25-27.
	Yu L L, Zhang M P, Wang K Y, et al. Research progress in ginsenoside biosynthesis regulation. Agriculture of Jinlin, 2014(5):25-27.
[5]	Wong A S T, Che C M, Leung K. Recent advances in ginseng as cancer therapeutics: a functional and mechanistic overview. Natural Product Reports, 2015,32(2):256-272. doi: 10.1039/c4np00080c pmid: 25347695
[6]	李伟娜, 蒋云云, 刘彦楠, 等. 人参皂苷单体定向转化的生物催化及应用进展. 生物工程学报, 2019,35(9):1590-1606.
	Li W N, Jiang Y Y, Liu Y N, et al. Biocatalytic strategies in producing ginsenoside by glycosidase-a review. Chinese Journal of Biotechnology, 2019,35(9):1590-1606.
[7]	张涛. 人参及其皂苷生物合成对低温的生理生态响应机制研究. 吉林:吉林农业大学, 2019.
	Zhang T. Physiological and ecological response mechanism of Panax ginseng and its saponins biosynthesis to low temperature. Jilin: Jilin Agricultural University, 2019.
[8]	黄再强, 朱琳, 高明菊, 等. 不同生长年限三七花的指纹图谱建立及其人参皂苷的含量比较研究. 中国药房, 2020,31(8):969-974.
	Huang Z Q, Zhu L, Gao M J, et al. Establishment of fingerprints and comparative study on ginsenoside content of panax notoginseng flower with different growing years. China Pharmacy, 2020,31(8):969-974.
[9]	薛海洁, 王颖, 李春. 植物天然产物的微生物合成与转化. 化工学报, 2019,70(10):3825-3835.
	Xue H J, Wang Y, Li C. Microbial synthesis and transformation of plant-derived natural products. CIESC Journal, 2019,70(10):3825-3835.
[10]	李晓军, 张万斌, 高栓虎. 复杂天然产物全合成:化学合成与生物合成结合的策略. 有机化学, 2018,38(9):2185-2198. doi: 10.6023/cjoc201806019
	Li X J, Zhang W B, Gao S H. Total synthesis of complex natural products: combination chemical synthesis and biosynthesis strategies. Chinese Journal of Organic Chemistry, 2018,38(9):2185-2198. doi: 10.6023/cjoc201806019
[11]	Rao S R, Ravishankar G A. Plant cell cultures: chemical factories of secondary metabolites. Biotechnology Advances, 2002,20(2):101-153. doi: 10.1016/s0734-9750(02)00007-1 pmid: 14538059
[12]	Dudareva N, Della P D. Plant metabolic engineering: future prospects and challenges. Current Opinion in Biotechnology, 2013,24(2):226-228.
[13]	池淏甜, 陈实. 基因组学技术解码天然产物合成. 生物工程学报, 2019,35(10):1889-1900.
	Chi H T, Chen S. Genomics decode natural products synthesis. Chinese Journal of Biotechnology, 2019,35(10):1889-1900.
[14]	程术, 邓子新, 卞光凯, 等. 萜类高效合成平台的搭建与萜类产物批量挖掘. 生命科学, 2019,31(5):449-457.
	Cheng S, Deng Z X, Bian G K, et al. Construction of high-efficient terpenoid platform and the application in terpenoid discovery. Chinese Bulletin Life Sciences, 2019,31(5):449-457.
[15]	张先恩. 中国合成生物学发展回顾与展望. 中国科学:生命科学, 2019,12:1543-1572.
	Zhang X E. Synthetic biology in China: review and prospects. Scientia sinica vitae, 2019,49(12):1543-1572.
[16]	Tian M, LI L N, Zheng R R, et al. Advances on hormone-like activity of Panax ginseng and ginsenosides. Chinese Journal of Natural Medicines, 2020,18(7):526-535.
[17]	Zhang Q, Wang X D, Lv L Y, et al. Antineoplastic activity, structural modification, synthesis and structure-activity relationship of dammarane-type ginsenosides: an overview. Current Organic Chemistry, 2019,23(5):503-516.
[18]	Zhan C S, Ahmed S, Hu S, et al. Cytochrome P450 CYP716A254 catalyzes the formation of oleanolic acid from beta-amyrin during oleanane-type triterpenoid saponins biosynthesis in Anemone flaccida. Biochemical and Biophysical Research Communications, 2018,495(1):1271-1277.
[19]	Tang Q Y, Chen G, Song W L, et al. Transcriptome analysis of Panax zingiberensis identifes genes encoding oleanolic acid glucuronosyltransferase involved in the biosynthesis of oleanane-type ginsenosides. Planta, 2019,249(2):393-406.
[20]	Li J, Ma L, Zhang S T, et al. Transcriptome analysis of 1-and 3-year-old Panax notoginseng roots and functional characterization of saponin biosynthetic genes DS and CYP716A47-like. Planta, 2019,249(2):1229-1237.
[21]	林廷文, 杜金法, 黄丽瑾, 等. 人参皂苷糖基转移酶基因研究概述. 中国中药杂志, 2020,45(19):4574-4581.
	Lin T W, Du J F, Huang L J, et al. Overview of research in ginsenosides glycosyltransferase. China Journal of Chinese Materia Medica, 2020,45(19):4574-4581.
[22]	Cheng Y, Liu H B, Tong X J, et al. Identification and analysis of CYP450 and UGT supergene family members from the transcriptome of Aralia elata (Miq.) seem reveal candidate genes for triterpenoid saponin biosynthesis. BMC Plant Biology, 2020,20(1):214.
[23]	马莹, 蔡媛, 马晓晶, 等. 药用植物活性成分生物合成中P450的研究进展. 药学学报, 2020,55(7):1573-1589.
	Ma Y, Cai Y, Ma X J, et al. Research progress of P450 in the biosynthesis of bioactive compound of medicinal plants. Acta Pharmaceutica Sinica, 2020,55(7):1573-1589.
[24]	Zhao J N, Wang R F, Zhao S J, et al. Advance in glycosyltransferases, the important bioparts for production of diversified ginsenosides. Chinese Journal of Natural Medicines, 2020,18(9):643-658.
[25]	Gu W, Geng C, Xue W D, et al. Characterization and function of the 3-hydroxy-3-methylglutaryl-CoA reductase gene in Alisma orientale (Sam.) Juz. and its relationship with protostane triterpene production. Plant Physiology and Biochemistry, 2015,97:378-389.
[26]	李佳秀, 蔡倩茹, 吴杰群. 萜类化合物在酿酒酵母中的合成生物学研究进展. 生物技术通报, 2020,36(12):199-207.
	Li J X, Cai Q R, Wu J Q. Research progress on the synthetic biology of terpenes in Saccharomyces cerevisiae. Biotechnology Bulletin, 2020,36(12):119-207.
[27]	Wei H, Xu C, Movahedi A, et al. Characterization and function of 3-hydroxy-3-methylglutaryl-CoA reductase in Populus trichocarpa: overexpression of PtHMGR enhances terpenoids in transgenic poplar. Frontiers in Plant Science, 2019,10:1476.
[28]	Rao S, Meng X X, Liao Y L, et al. Characterization and functional analysis of two novel 3-hydroxy-3-methylglutaryl-coenzyme A reductase genes (GbHMGR2 and GbHMGR3) from Ginkgo biloba. Scientific Reports, 2019,9(1):14109.
[29]	李志红, 段佩玲, 徐静雅, 等. 山茱萸萜类合成途径关键酶HMGR1基因的克隆与分析. 中草药, 2020,51(18):4733-4738.
	Li Z H, Duan P L, Xu J Y, et al. Cloning and analysis of a key enzyme of HMGR1 gene involved in terpene biosynthesis of Cornus officinalis. Chinese Traditional and Herbal Drugs, 2020,51(18):4733-4738.
[30]	荆礼, 赵欢, 莫长明, 等. 罗汉果3-羟基-3-甲基戊二酰辅酶A还原酶基因的克隆及表达分析. 中国中药杂志, 2020,45(20):4875-4881.
	Jin L, Zhao H, Mo C M, et al. Cloning and expression analysis of 3-hydroxy-3-methylglutaryl coenzyme a reductase genes from Siraitia grosvenorii. China Journal of Chinese Materia Medica, 2020,45(20):4875-4881.
[31]	陈丽娜, 万倩芸, 邓娟, 等. 茅苍术两个HMGR基因(AlHMGR)的克隆与分析. 基因组学与应用生物学, 2020,39(4):1732-1740.
	Chen L N, Wan Q Y, Deng J, et al. Cloning and analysis of two HMGR genes (AlHMGR) in atractylodes lancea. Genomics and Applied Biology, 2020,39(4):1732-1740.
[32]	王丽平, 谌琴琴, 梁瑾, 等. 千里光法尼基焦磷酸合酶基因的克隆及功能鉴定. 中国中药杂志, 2020,45(23):5677-5685.
	Wang L P, Zhan Q Q, Liang J, et al. Cloning and functional characterization of farnesyl diphosphate synthase in Senecio scandens. China Journal of Chinese Materia Medica, 2020,45(23):5677-5685.
[33]	张志勇, 陈莹, 江学波, 等. 暗紫贝母FPS基因克隆与表达特性分析. 种子, 2019,38(11):39-45.
	Zhang Z Y, Chen Y, Jiang X B, et al. Cloning and expression analysis of farnesyl pyrophosphate synthase gene in Fritillaria unibracteata. Seed, 2019,38(11):39-45.
[34]	Xia P G, Zheng Y J, Liang Z S. Structure and location studies on key enzymes in saponins biosynthesis of panax notoginseng. International Journal of Molecular Sciences, 2019,20(24):6121.
[35]	许小向, 尹忠平, 刘泽波, 等. 青钱柳鲨烯合成酶(CpSS)全长基因的克隆、分析与表达. 中国食品学报, 2020,20(2):111-119.
	Xu X X, Yin Z P, Liu Z B, et al. Cloning, analysis and expression of the squalene synthase in cyclocarya paliurus. Journal of Chinese Institute of Food Science and Technology, 2020,20(2):111-119.
[36]	王丽君, 李艳青, 谢舒平, 等. 基于转录组测序黑老虎角鲨烯合酶基因克隆和生物信息学分析. 中药新药与临床药理, 2019,30(7):870-878.
	Wang L J, Li Y Q, Xie S P, et al. Cloning and bioinformatics analysis of squalene synthase(KcSQS)gene from kadsura coccinea (Lem.) A.C.smith based on transcriptome sequencing. Traditional Chinese Drug Research and Clinical Pharmacology, 2019,30(7):870-878.
[37]	Gao R, Yu D, Chen L L, et al. Cloning and functional analysis of squalene synthase gene from Dryopteris fragrans (L.) Schott. Protein Expressin and Purification, 2019,155:95-103.
[38]	Chen G S, Yu W J, Ke L L, et al. Cloning and analyzing a squalene synthase gene in Pseudostellaria heterophylla. Gene Reports, 2018,12:39-46. doi: 10.1016/j.genrep.2018.06.001
[39]	Hou X J, Tai Y L, Ling S P, et al. Molecular cloning and characterization of squalene synthase from Matricaria recutita L. Acta Physiologiae Plantarum, 2018,40:103.
[40]	李晶, 林雄杰, 王泽辉, 等. 牛樟芝鲨烯环氧酶基因的克隆、生物信息学及表达分析. 中草药, 2018,49(10):2440-2446.
	Li J, Lin X J, Wang Z H, et al. Cloning,bioinformatics,and expression analysis of squalene epoxidase in Antrodia cinnamomea. Chinese Traditional and Herbal Drugs, 2018,49(10):2440-2446.
[41]	梁娥, 齐敏杰, 张来. 竹节参鲨烯环氧酶基因的克隆与生物信息学分析. 基因组学与应用生物学, 2020, http://kns.cnki.net/kcms/detail/45.1369.q.20200525.1353.002.html.
	Liang E, Qi M J, Zhang L. Molecular cloning and sequences analysis of SE gene from panax japonicus. Genomics and Applied Biology, 2020, http://kns.cnki.net/kcms/detail/45.1369.q.20200525.1353.002.html.
[42]	Zhu L, Ma L Q, Xu F, et al. Cloning and expression analysis of a squalene epoxidase gene from ginkgo biloba. Notulae Botanicae Horti Agrobotanici Cluj-Napoca, 2018,46(1):39-44.
[43]	张莹, 王广, 左天, 等. 人参属植物达玛烷合成酶基因的生物信息学分析. 武汉轻工大学学报, 2019,38(2):25-30.
	Zhang Y, Wang G, Zuo T, et al. Bioinformatics analysis of dammarane saponin gene in Panax genus. Journal of Wuhan Polytechnic University, 2019,38(2):25-30.
[44]	赵志新, 王星星. 植物三萜皂苷代谢中达玛烷合成酶和β-香树脂合成酶的生物信息学分析. 江苏农业科学, 2019,47(18):86-92.
	Zhao Z X, Wang X X. Bioinformatics analysis of DS and β-AS in metabolism of triterpenoid saponins in plants. Jiangsu Agricultural Sciences, 2019,47(18):86-92.
[45]	王景思, 吴亚运, 黄丽芬, 等. 竹节参达玛烷合成酶基因的克隆和生物信息学分析. 基因组学与应用生物学, 2020,39(7):3151-3158.
	Wang J S, Wu Y Y, Huang L F, et al. Cloning of dammarenediol synthase gene from panax japonicus C.A.mey and its bioinformatics analysis. Genomics and Applied Biology, 2020,39(7):3151-3158.
[46]	Hu T, Liu Z Z, Tian S K, et al. Polymorphism of β-amyrin synthase gene (β-AS) influence the accumulation of triterpenes in licorice. South African Journal of Botany, 2019,125:310-20.
[47]	孙化鹏, 钟晓红, 徐子健, 等. 洋常春藤β-AS基因的全长克隆与表达分析. 分子植物育种, 2018,16(3):733-739.
	Sun H P, Zhong X H, Xu Z J, et al. Cloning and expression analysis of β-AS gene in hedera helix L. Molecular Plant Breeding, 2018,16(3):733-739.
[48]	胡艳, 廖应镇, 陈奇聪, 等. 绞股蓝β-香树脂醇合酶基因的克隆和序列分析. 基因组学与应用生物学, 2019,38(7):3273-3279.
	Hu Y, Liao Y Z, Chen Q C, et al. Cloning and sequence analysis of β-Amyrin synthase gene from gynostemma pentaphyllum. Genomics and Applied Biology, 2019,38(7):3273-3279.
[49]	Li J C, Wang C, Qi W J, et al. Cloning and functional characterization of the beta-amyrin synthase gene from Bupleurum chinense. Biologia Plantarum, 2020,64:314-319.
[50]	朱灵英, 郭娟, 张爱丽, 等. 参与植物三萜生物合成的细胞色素P450酶研究进展. 中草药, 2019,50(22):5597-5610.
	Zhu L Y, Guo J, Zhang A L, et al. Research progress on CYP450 involved in medicinal plant triterpenoid biosynthesis. Chinese Traditional and Herbal Drugs, 2019,50(22):5597-5610.
[51]	赵志新, 鹿鹏鹏, 王通. 植物三萜皂苷代谢中细胞色素P450的生物信息学分析. 西南农业学报, 2019,32(10):2304-2312.
	Zhao Z X, Lu P P, Wang T. Bioinformatics analysis of cytochrome P450 in triterpenoid saponins metabolism in plants. Southwest China Journal of Agricultural Sciences, 2019,32(10):2304-2312.
[52]	Rahimi S, Kim J, Mijakovic I, et al. Triterpenoid-biosynthetic UDP-glycosyltransferases from plants. Biotechnology Advances, 2019,37(7):107394.
[53]	Yin J, Li Y, Li C X, et al. Cloning, expression characteristics of a new FPS gene from birch (Betula platyphylla suk.) and functional identification in triterpenoid synthesis. Industrial Crops and Products. 2020,154:112591.
[54]	Abbas F, Ke Y G, Zhou Y W, et al. Cloning, functional characterization and expression analysis of LoTPS5 from Lilium ‘Siberia’. Gene, 2020,756:144921. pmid: 32593719
[55]	Zhang B, Chen L, Huo Y B, et al. Enhanced production of celastrol in Tripterygium wilfordii hairy root cultures by overexpression of TwSQS2. Biochemical Engineering Journal, 2020,161:107681.
[56]	Liu Y, Zhou J W, Hu T Y, et al. Identification and functional characterization of squalene epoxidases and oxidosqualene cyclases from Tripterygium wilfordii. Plant Cell Reports, 2020,39(3):409-418. doi: 10.1007/s00299-019-02499-7 pmid: 31838574
[57]	Lu X, Zhang L N, Du J F, et al. Comparative analysis and natural evolution of squalene epoxidase in three Fritillaria species. Plant Molecular Biology, 2020,103(6):705-718. pmid: 32577984
[58]	Li J C, Wang C, Qi W T, et al. Cloning and functional characterization of the β-amyrin synthase genefrom Bupleurum chinense. Biologia Plantarum, 2020,64:314-319.
[59]	Xu S, Zhao C L, Wen G S, et al. Longitudinal expression patterns of HMGR, FPS, SS, SE and DS and their correlations with saponin contents in green-purple transitional aerial stems of Panax notoginseng. Industrial Crops and Products, 2018,119:132-143.
[60]	刘啸尘, 刘护, 张良, 等. 细胞代谢过程中的酶促糖基化及其功能. 中国生物工程杂志. 2018,38(1):69-77.
	Liu X C, Liu H, Zhang L, et al. Enzymatic glycosylation and its function in metabolic process of cells. China Biotechnology, 2018,38(1):69-77.
[61]	Zeng X, Luo T, Li J J, et al. Transcriptomics-based identification and characterization of 11 CYP450 genes of Panax ginseng responsive to MeJA. Acta Biochimica et Biophysica Sinica, 2018,50(11):1094-1103.
[62]	Ma W, Zhao L, Ma Y D, et al. Oriented efficient biosynthesis of rare ginsenoside Rh2 from PPD by compiling UGT-Yjic mutant with sucrose synthase. International Journal of Biological Macromolecules, 2020,146:853-859.
[63]	Hu Y M, Xue J, Min J, et al. Biocatalytic synthesis of ginsenoside Rh2 using Arabidopsis thaliana glucosyltransferase-catalyzed coupled reactions. Journal of Biotechnology, 2020,309:107-112.
[64]	张亦男, 刘振, 毛相朝. 大肠杆菌角鲨烯合成途径的构建与调控. 工业微生物, 2019,49(3):1-6.
	Zhang Y N, Liu Z, Mao X C. Construction and regulation of squalene synthesis pathway in Escherichia coli. Industrial Microbiology, 2019,49(3):1-6.
[65]	Zhu F Y, Zhong X F, Hu M Z, et al. In vitro reconstitution of mevalonate pathway and targeted engineering of farnesene overproduction in Escherichia coli. Biotechnology and Bioengineering, 2014,111(7):1396-1405.
[66]	Song Y F, Guan Z, Merkerk R V, et al. Production of squalene in Bacillus subtilis by squalene synthase screening and metabolic engineering. Journal of Agricultural and Food Chemistry. 2020,68(15):4447-4455.
[67]	Zhao C C, Gao X, Liu X B, et al. Enhancing biosynthesis of a ginsenoside precursor by self-assembly of two key enzymes in Pichia pastoris. Journal of Agricultural and Food Chemistry, 2016,64(17):3380-3385. pmid: 27074597
[68]	Wu Y F, Xu S, Gao X, et al. Enhanced protopanaxadiol production from xylose by engineered Yarrowia lipolytica. Microbial Cell Factories, 2019,18(1):83. doi: 10.1186/s12934-019-1136-7 pmid: 31103047
[69]	Li D S, Wu Y F, Zhang C B, et al. Production of triterpene ginsenoside compound K in the non-conventional Yeast Yarrowia lipolytica. Journal of Agricultural and Food Chemistry, 2019,67(9):2581-2588.
[70]	Wei W, Wang P P, Wei Y J, et al. Characterization of panax ginseng UDP-glycosyltransferases catalyzing protopanaxatriol and biosyntheses of bioactive ginsenosides F1 and Rh1 in metabolically engineered Yeasts. Molecular Plant, 2015,8(9):1412-1424.
[71]	Zhuang Y, Yang G Y, Chen X H, et al. Biosynthesis of plant-derived ginsenoside Rh2 in yeast via repurposing a key promiscuous microbial enzyme. Metabolic Engineering, 2017,42:25-32.
[72]	Wang P P, Wei Y J, Fan Y et al. Production of bioactive ginsenosides Rh2 and Rg3 by metabolically engineered yeasts. Metabolic Engineering, 2015,29:97-105.
[73]	Hu Z F, Gu A D, Liang L, et al. Construction and optimization of microbial cell factories for sustainable production of bioactive dammarenediol-II glucosides. Green Chemistry, 2019,21(12):3286-3299.
[74]	Wang P P, Wei W, Ye W, et al. Synthesizing ginsenoside Rh2 in Saccharomyces cerevisiae cell factory at high-efficiency. Cell Discovery, 2019,5:5. pmid: 30652026
[75]	谢泽雄, 陈祥荣, 肖文海, 等. 基因组再造与重排构建细胞工厂. 化工学报, 2019,70(10):3712-3721.
	Xie Z X, Chen X R, Xiao W H, et al. Cell factory construction accelerated by genome synthesis and rearrangement. CIESC Journal, 2019,70(10):3712-3721.
[76]	王文方, 钟建江. 合成生物学驱动的智能生物制造研究进展. 生命科学, 2019,31(4):413-422.
	Wang W F, Zhong J J. Recent advances in smart biomanufacturing driven by synthetic biology. Chinese Bulletin of Life Sciences, 2019,31(4):413-422.
[77]	Zhang G L, Cao Q, Liu J Z, et al. Refactoring β‐amyrin synthesis in Saccharomyces cerevisiae. Aiche Journal, 2015,61(10):3172-3179.
[78]	Kim J E, Jang I S, Sung B H, et al. Rerouting of NADPH synthetic pathways for increased protopanaxadiol production in Saccharomyces cerevisiae. Scientific Reports, 2018,8(1):15820.
[79]	汪莲, 王浩君, 罗云孜. CRISPR技术在微生物合成生物学中的应用. 生命科学, 2019,31(5):493-507.
	Wang L, Wang H J, Luo Y Z. Application of CRISPR technology in synthetic microbial biology. Chinese Bulletin of Life Sciences, 2019,31(5):493-507.

[1]	张恒,刘慧燕,潘琳,王红燕,李晓芳,王彤,方海田. 生物法合成γ-氨基丁酸的研究策略^*[J]. 中国生物工程杂志, 2021, 41(8): 110-119.
[2]	李冰,张传波,宋凯,卢文玉. 生物合成稀有人参皂苷的研究进展^*[J]. 中国生物工程杂志, 2021, 41(6): 71-88.
[3]	苗轶男,李敬知,王帅,李春,王颖. 萜烯生物合成中关键酶的研究进展^*[J]. 中国生物工程杂志, 2021, 41(6): 60-70.
[4]	翟君叶,成旭,孙泽敏,李春,吕波. 毛蕊花糖苷的生物合成研究进展[J]. 中国生物工程杂志, 2021, 41(5): 94-104.
[5]	王光路, 王梦园, 周忆菲, 马科, 张帆, 杨雪鹏. 吡咯喹啉醌生物合成研究进展 ^*[J]. 中国生物工程杂志, 2021, 41(1): 103-113.
[6]	郭二鹏, 张建志, 司同. 羊毛硫肽的高通量工程改造方法新进展 ^*[J]. 中国生物工程杂志, 2021, 41(1): 30-41.
[7]	饶海密,梁冬梅,李伟国,乔建军,财音青格乐. 真菌芳香聚酮化合物的合成生物学研究进展^*[J]. 中国生物工程杂志, 2020, 40(9): 52-61.
[8]	段海荣,魏赛金,黎循航. 铜绿假单胞菌中鼠李糖脂生物合成的研究进展^*[J]. 中国生物工程杂志, 2020, 40(9): 43-51.
[9]	邓廷山,武国干,孙宇,唐雪明. 苯乳酸生物合成的研究进展^*[J]. 中国生物工程杂志, 2020, 40(9): 62-68.
[10]	闫伟欢,黄统,洪解放,马媛媛. 丁醇在大肠杆菌中的生物合成研究进展^*[J]. 中国生物工程杂志, 2020, 40(9): 69-76.
[11]	高小朋,何猛超,许可,李春. 工业微生物发酵过程中pH调控研究进展 ^*[J]. 中国生物工程杂志, 2020, 40(6): 93-99.
[12]	刘金丛,刘雪,於洪建,赵广荣. 微生物合成根皮素及其糖苷研究进展 ^*[J]. 中国生物工程杂志, 2020, 40(10): 76-84.
[13]	欧梦莹,王晓政,林双君,关统伟,林宜锦. 链黑菌素研究进展 ^*[J]. 中国生物工程杂志, 2019, 39(7): 100-107.
[14]	马雅婷,刘珍宁,刘雪,於洪建,赵广荣. 微生物异源合成植物异喹啉生物碱的新进展 ^*[J]. 中国生物工程杂志, 2019, 39(11): 123-131.
[15]	于思礼,刘雪,张昭宇,於洪建,赵广荣. 甜菜素的生物合成及其代谢调控进展 ^*[J]. 中国生物工程杂志, 2018, 38(8): 84-91.

Viewed

Full text

Abstract

Cited

Shared

Discussed