Recent Advances in Yeast Recombinant Biosynthesis of the Triterpenoid Protopanaxadiol and Glycosylated Derivatives Thereof

Abstract

Plant natural products are a seemingly endless resource for novel chemical structures. However, their extraction often results in high prices, fluctuation in both quantity and quality, and negative environmental impact. The latter might result from the extraction procedure but more often from the high amount of plant biomass required. With the advent of synthetic biology, producing natural plant products in large quantities using yeasts as hosts has become possible. Here, we focus on the recent advances in metabolic engineering of the yeasts species Saccharomyces cerevisiae and Yarrowia lipolytica for the synthesis of ginsenoside triterpenoids, namely, dammarenediol-II, protopanaxadiol, protopanaxatriol, compound K, ginsenoside Rh1, ginsenoside Rh2, ginsenoside Rg3, and ginsenoside F1. A discussion is provided on advanced synthetic biology, bioprocess strategies, and current challenges for the biosynthesis of ginsenoside triterpenoids. Finally, future directions in metabolic and process engineering are summarized and may help reify sustainable ginsenoside production.

Bioprocess optimization enables enhanced protopanaxadiol production in yeast

“…25 Furthermore, NADPH is oxidized to NADP by a P450 reductase in the presence of oxygen, then transfers electrons to the monooxygenases, such as PPDS. 7 Therefore, controlling the oxygen concentration will also play a critical role in synthesizing the final product. Consequently, in the subsequent investigation, we selected glucose, glutamate, salts, temperature, and oxygen as the main significant factors for further research to check if these factors will affect the final PPD and DM production.…”

“…Ethanol is a more reduced carbon source than glucose, which feeds directly into the cytosolic acetyl-CoA pool required for the mevalonate pathway. 7 Therefore, we also measured the concentration of the carbon sources and triterpenoid products during the fermentation to investigate the fermentation kinetics of PPD and DM. As a Crabtree-positive yeast, the engineered S. cerevisiae uses respiro-fermentative glucose metabolism and produces ethanol and carbon dioxide.…”

“…2,3,4 More than 180 ginsenosides have been identified in the Panax genus, which can be categorized into two groups based on their aglycones: dammarane-type tetracyclic and oleanane-type pentacyclic ginsenosides. 5,6,7 Dammarane-type tetracyclic ginsenosides can be further divided into three groups, ocotillol, protopanaxadiol (PPD)-type ginsenosides, and protopanaxatriol (PPT)-type ginsenosides, based on the carbohydrate moieties at C3, C6, and C20 positions and the respective hydroxylation. 7 Ginseng has been used in traditional herbal medicine in Asia for more than 4,000 years.…”

“…5,6,7 Dammarane-type tetracyclic ginsenosides can be further divided into three groups, ocotillol, protopanaxadiol (PPD)-type ginsenosides, and protopanaxatriol (PPT)-type ginsenosides, based on the carbohydrate moieties at C3, C6, and C20 positions and the respective hydroxylation. 7 Ginseng has been used in traditional herbal medicine in Asia for more than 4,000 years. 5,8,3 The term "ginseng" is derived from the Chinese words "人 參 (Renshen)", "the essence of men", indicating its importance.…”

Synthesis and Fabrication of Betulin-Derived Polysulfide and Polysulfoxide Electrospun Fibers for Fruit Preservation

“…Terpenes and their derivatives, known for their abundance and affordability, serve as an excellent resource for the production of biobased polymeric materials . These biocompounds, naturally occurring in plants, fruits, vegetables, herbs, and spices, contribute to their characteristic aromas and flavors. − Additionally, they possess notable pharmacological properties, such as antibacterial activity, making them essential in various everyday life and industrial applications. − The unique characteristics of terpenes have been harnessed to develop sustainable polymeric materials with diverse biomedical applications . For instance, cis -1,4-polyisoprene, also referred to as natural rubber, offers a range of sustainable monomers, including the 1,3-diene monomers β-myrcene and β-farnesene, and serves as an example of terpene-based building blocks for functional polymers .…”