Microorganisms for Ginsenosides Biosynthesis: Recent Progress, Challenges, and Perspectives

Abstract

Ginsenosides are major bioactive compounds present in the Panax species. Ginsenosides exhibit various pharmaceutical properties, including anticancer, anti-inflammatory, antimetastatic, hypertension, and neurodegenerative disorder activities. Although several commercial products have been presented on the market, most of the current chemical processes have an unfriendly environment and a high cost of downstream processing. Compared to plant extraction, microbial production exhibits high efficiency, high selectivity, and saves time for the manufacturing of industrial products. To reach the full potential of the pharmaceutical resource of ginsenoside, a suitable microorganism has been developed as a novel approach. In this review, cell biological mechanisms in anticancer activities and the present state of research on the production of ginsenosides are summarized. Microbial hosts, including native endophytes and engineered microbes, have been used as novel and promising approaches. Furthermore, the present challenges and perspectives of using microbial hosts to produce ginsenosides have been discussed.

Keywords: Panax species; endophytes; engineered microorganisms; ginsenosides.

Figure 1

Biological activities and cellular mechanisms versus cancer of ginsenosides. CDK: cyclin-dependent kinase; IAP: inhibitory apoptotic protein; VEGF-A: vascular endothelial growth factor A; FGF-2: fibroblast growth factor 2; PI3K/AKT: protein kinase B signaling pathway; TSP-1: inhibitors thrombospondin-1; IGF-1: insulin-like growth factor-1; TNF-α: tumor necrosis factor-α; MMP: matrix metalloproteinase; NF-κB, nuclear factor κB.

Figure 2

Bioproduction of ginsenosides by endophytes. (A) Native endophytes as biological source of ginsenosides; (B) Biosynthesis of ginsenosides from major ginsenosides through biotransformation.

Figure 3

Biosynthetic pathway for ginsenoside production in cytosol of engineered yeasts. Enzymes: ACS, acetyl-CoA synthase; ALD6, acetaldehyde dehydrogenases encoding by ald6; beta-AS, β-amyrin synthase; CPR, cytochrome P450 reductase; CS, cycloartenol synthase; DDS, dammarenediol-II synthase; ERG1, squalene epoxidase; ERG7, lanosterol synthase; ERG8, phosphomevalonate kinase; ERG9, squalene synthase; ERG10, acetyl-CoA C-acetyltransferase; ERG12, mevalonate kinase; ERG13, HMG-CoA synthase; ERG19, diphosphomevalonate; ERG20, farnesyl-diphosphate synthase; IDI, isopentenyl diphosphate-isomerase; HMG, 3-hydroxy-3-methylglutaryl-CoA reductase; OAS, oleanolic acid synthase; PPTS, protopanaxatriol synthase; XDH, xylitol dehydrogenase; XKS, Xylulose kinase; XR, xylose reductase.

Figure 4

Processing and future perspective of production ginsenosides by microbial hosts.