Recent Advances in the Metabolic Engineering of Yeasts for Ginsenoside Biosynthesis

Abstract

Ginsenosides are a group of glycosylated triterpenes isolated from Panax species. Ginsenosides are promising candidates for the prevention and treatment of cancer as well as food additives. However, owing to a lack of efficient approaches for ginsenoside production from plants and chemical synthesis, ginsenosides may not yet have reached their full potential as medicinal resources. In recent years, an alternative approach for ginsenoside production has been developed using the model yeast Saccharomyces cerevisiae and non-conventional yeasts such as Yarrowia lipolytica and Pichia pastoris. In this review, various metabolic engineering strategies, including heterologous gene expression, balancing, and increasing metabolic flux, and enzyme engineering, have been described as recent advanced engineering techniques for improving ginsenoside production. Furthermore, the usefulness of a systems approach and fermentation strategy has been presented. Finally, the present challenges and future research direction for industrial cell factories have been discussed.

Development of synthetic biology tools to engineer Pichia pastoris as a chassis for the production of natural products

“…Dammarenediol-II is a triterpenoid with multiple pharmacological activities. On the basis of the natural triterpene biosynthesis pathway [ 80 , 81 ], Liu et al introduced PgDDS from Panax ginseng , encoding a dammarenediol-II synthase that catalyzed the production of dammarenediol-II from 2,3-oxidosqualene, to successfully construct a dammarenediol-II producing P. pastoris strain ( Fig. 3 ).…”

Medicinal Plants: Guests and Hosts in the Heterologous Expression of High-Value Products

“…Plant [7,117] for the condensation of dopamine and 4-hydroxyphenylacetaldehyde to (S)-norcoclaurine from which all BIAs are derived. The reduced sequencing costs and bioinformatics tools advancements led to the increased quantity of whole-genome sequences of medicinal plants in recent years [24].…”

“…Medicinal Plants: Guests and Hosts in the Heterologous Expression of High-Value Products tively more expensive (25-57 USD/mg) in comparison to the cost of yeast-produced ginsenosides (0.5-25 USD/mg) [7]. Numerous natural products are also derived from plant foods and have additional health benefits beyond their basic nutritional value, thus preventing a wide range of chronic diseases [8].…”

CRISPRi-Guided Metabolic Flux Engineering for Enhanced Protopanaxadiol Production in Saccharomyces cerevisiae

“…To overcome this, PPD and ginsenosides have been produced using de novo biosynthetic pathways in heterologous microbial organisms, including yeast [ 7 , 8 , 9 , 10 , 11 , 12 ]. PPD is biosynthesized from 2,3-oxidosqualene, which is derived from isopentenyl diphosphate and dimethylallyl diphosphate ([ 13 ]. These precursors are synthesized via the mevalonate (MVA) pathway in both ginseng and yeast [ 14 ].…”