Metabolic engineering of Saccharomyces cerevisiae for production of ginsenosides

Metab Eng. 2013 Nov;20:146-56. doi: 10.1016/j.ymben.2013.10.004. Epub 2013 Oct 11.

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.

Keywords: Dammarenediol-II; Ginsenosides; Metabolic engineering; Protopanaxadiol; Saccharomyces cerevisiae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / biosynthesis*
  • Arabidopsis / enzymology
  • Arabidopsis / genetics
  • Ginsenosides* / biosynthesis
  • Ginsenosides* / genetics
  • Metabolic Engineering*
  • Panax / enzymology
  • Panax / genetics
  • Plant Proteins / biosynthesis
  • Plant Proteins / genetics
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Ginsenosides
  • Plant Proteins
  • Recombinant Proteins