title: Metabolic engineering of Saccharomyces cerevisiae for production of ginsenosides.
abstract: Ginsenosides are the primary bioactive components of ginseng, which is a popular medicinal herb and exhibits diverse pharmacological activities. Protopanaxadiol is the aglycon of several dammarane-type ginsenosides, which also has anticancer activity. For microbial production of protopanaxadiol, dammarenediol-II synthase and protopanaxadiol synthase genes of Panax ginseng, together with a NADPH-cytochrome P450 reductase gene of Arabidopsis thaliana, were introduced into Saccharomyces cerevisiae, resulting in production of 0.05 mg/g DCW protopanaxadiol. Increasing squalene and 2,3-oxidosqualene supplies through overexpressing truncated 3-hydroxyl-3-methylglutaryl-CoA reductase, farnesyl diphosphate synthase, squalene synthase and 2,3-oxidosqualene synthase genes, together with increasing protopanaxadiol synthase activity through codon optimization, led to 262-fold increase of protopanaxadiol production. Finally, using two-phase extractive fermentation resulted in production of 8.40 mg/g DCW protopanaxadiol (1189 mg/L), together with 10.94 mg/g DCW dammarenediol-II (1548 mg/L). The yeast strains engineered in this work can serve as the basis for creating an alternative way for production of ginsenosides in place of extraction from plant sources.
authors.affiliation: Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, China; Key Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, China.
authors.forename: Zhubo
authors.initials: Z
authors.lastname: Dai
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Xianan
authors.initials: X
authors.lastname: Zhang
authors.forename: Mingyu
authors.initials: M
authors.lastname: Shi
authors.forename: Beibei
authors.initials: B
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Luqi
authors.initials: L
authors.lastname: Huang
authors.forename: Xueli
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000096:biosynthesis*; D017360:Arabidopsis / Q000201:enzymology / Q000235:genetics; D036145:Ginsenosides / Q000096:biosynthesis / Q000235:genetics; D060847:Metabolic Engineering; D005894:Panax / Q000201:enzymology / Q000235:genetics; D010940:Plant Proteins / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D036145:Ginsenosides; D010940:Plant Proteins; D011994:Recombinant Proteins
keywords: Dammarenediol-II; Ginsenosides; Metabolic engineering; Protopanaxadiol; Saccharomyces cerevisiae