气候变化领域集成服务门户(CCPortal): Complete biosynthesis of the potential medicine icaritin by engineered Saccharomyces cerevisiae and Escherichia coli

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DOI	10.1016/j.scib.2021.03.002
	Complete biosynthesis of the potential medicine icaritin by engineered Saccharomyces cerevisiae and Escherichia coli
	Wang P.; Li C.; Li X.; Huang W.; Wang Y.; Wang J.; Zhang Y.; Yang X.; Yan X.; Wang Y.; Zhou Z.
发表日期	2021
ISSN	20959273
英文摘要	Icaritin is a prenylflavonoid present in the Chinese herbal medicinal plant Epimedium spp. and is under investigation in a phase III clinical trial for advanced hepatocellular carcinoma. Here, we report the biosynthesis of icaritin from glucose by engineered microbial strains. We initially designed an artificial icaritin biosynthetic pathway by identifying a novel prenyltransferase from the Berberidaceae-family species Epimedium sagittatum (EsPT2) that catalyzes the C8 prenylation of kaempferol to yield 8-prenlykaempferol and a novel methyltransferase GmOMT2 from soybean to transfer a methyl to C4’-OH of 8-prenlykaempferol to produce icaritin. We next introduced 11 heterologous genes and modified 12 native yeast genes to construct a yeast strain capable of producing 8-prenylkaempferol with high efficiency. GmOMT2 was sensitive to low pH and lost its activity when expressed in the yeast cytoplasm. By relocating GmOMT2 into mitochondria (higher pH than cytoplasm) of the 8-prenylkaempferol–producing yeast strain or co-culturing the 8-prenylkaempferol–producing yeast with an Escherichia coli strain expressing GmOMT2, we obtained icaritin yields of 7.2 and 19.7 mg/L, respectively. Beyond the characterizing two previously unknown plant enzymes and conducting the first biosynthesis of icaritin from glucose, we describe two strategies of overcoming the widespread issue of incompatible pH conditions encountered in basic and applied bioproduction research. Our findings will facilitate industrial-scale production of icaritin and other prenylflavonoids. © 2021 Science China Press
英文关键词	Biochemistry; Biosynthesis; Cytology; Enzymes; Escherichia coli; Flavonoids; Glucose; Yeast; Biosynthetic pathway; Cerevisiae; Clinical trial; Epimedium; Hepatocellular carcinoma; Medicinal plants; Microbial strain; Prenylflavonoid; Saccharomyces; Yeast strain; Genes
语种	英语
来源期刊	Science Bulletin
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/207593
作者单位	CAS-Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, 200032, China; University of Chinese Academy of Sciences, Beijing, 100049, China; Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan, 430074, China; School of Life Sciences, Henan University, Kaifeng, 475001, China; Key Laboratory of South China Agricultural Plant Molecular Analysis and Genetic Improvement, Center of Economic Botany/Core Botanical Gardens, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou, 510650, China
推荐引用方式 GB/T 7714	Wang P.,Li C.,Li X.,et al. Complete biosynthesis of the potential medicine icaritin by engineered Saccharomyces cerevisiae and Escherichia coli[J],2021.
APA	Wang P..,Li C..,Li X..,Huang W..,Wang Y..,...&Zhou Z..(2021).Complete biosynthesis of the potential medicine icaritin by engineered Saccharomyces cerevisiae and Escherichia coli.Science Bulletin.
MLA	Wang P.,et al."Complete biosynthesis of the potential medicine icaritin by engineered Saccharomyces cerevisiae and Escherichia coli".Science Bulletin (2021).