Metabolic engineering of Saccharomyces cerevisiae for production of ginsenosides

Dai, Zhaoli; Liu, Yi; Zhang, Xianan; Shi, Mingyu; Wang, Beibei; Wang, Dong; Huang, Luqi; Zhang, Xueli

doi:10.1016/j.ymben.2013.10.004

Cited by 209 publications

(181 citation statements)

References 64 publications

Supporting

Mentioning

174

Contrasting

Unclassified

Order By: Relevance

“…Cell biomass was determined by spectrophotometer under 600 nm and convert to dry cell weight (1 OD 600 ¼0.513 g DCW L À 1 ) (Dai et al, 2013). The cell pellets were harvested, disrupted and extracted with n-butanol and used for the analysis of intracellular dammarane-type triterpenoids (dammarenediol II, PPD, Rh2 and Rg3).…”

Section: Yeast Cultivation and Metabolite Extractionmentioning

confidence: 99%

Production of bioactive ginsenosides Rh2 and Rg3 by metabolically engineered yeasts

Wang

Wei

Fan

et al. 2015

Metabolic Engineering

165

128

View full text Add to dashboard Cite

Section: Yeast Cultivation and Metabolite Extractionmentioning

confidence: 99%

Production of bioactive ginsenosides Rh2 and Rg3 by metabolically engineered yeasts

Wang

Wei

Fan

et al. 2015

Metabolic Engineering

165

128

View full text Add to dashboard Cite

“…In plants and microorganisms, cytochrome P450 enzymes take part in oxidation reactions that frequently function as a priming event for subsequent enzymatic conversions of the terpene structure (Alonso- Gutierrez et al, 2013;Dai et al, 2013;Hofer et al, 2013;Wriessnegger et al, 2014). However, identification of the P450 enzymes responsible for the biosynthesis of specific metabolites is difficult due to the large size and diversity of the P450 gene family, impeding efforts to reconstruct Table 2 Terpene titers obtained in AM102 cells carrying the indicated module-specific parts, together with Erg20p-CcGGPPS as the M1-specific part.…”

Section: Expanding the Diversity Of Terpene Structures Through The Inmentioning

confidence: 99%

Reconstructing the chemical diversity of labdane-type diterpene biosynthesis in yeast

Ignea

Iοannou

Georgantea

et al. 2015

Metabolic Engineering

View full text Add to dashboard Cite

Terpenes are a large class of natural products, many of which are used in cosmetics, pharmaceuticals, or biofuels. However, terpene's industrial application is frequently hindered by limited availability of natural sources or low yields of chemical synthesis. In this report, we developed a modular platform based on standardized and exchangeable parts to reproduce and potentially expand the diversity of terpene structures in Saccharomyces cerevisiae. By combining different module-specific parts, we exploited the substrate promiscuity of class I diterpene synthases to produce an array of labdane-type scaffolds. These were subsequently modified by a scaffold decoration module consisting of a mutant library of a promiscuous cytochrome P450 to afford a range of hydroxylated diterpenes. Further P450 protein engineering yielded dedicated and efficient catalysts for specific products. Terpenes produced include precursors of pharmacologically important compounds, molecules that are difficult to obtain from natural sources, or new natural products. The approach described here provides a platform on which additional gene mining, combinatorial biosynthesis, and protein engineering efforts can be integrated to sustainably explore the terpene chemical space.

show abstract

“…Consequently, industrial production relies on extraction from the plant, but these compounds are often produced in small quantities as complex mixtures, making isolation challenging, laborious, and expensive (8)(9)(10). Reconstitution of plant pathways in microbial hosts is proving to be a promising approach to access plant-derived compounds as evidenced by the successful production of terpenes, flavonoids, and benzylisoquinoline alkaloids in microorganisms (11)(12)(13)(14)(15)(16)(17)(18)(19). Microbial hosts can also be used to construct hybrid biosynthetic pathways to generate modified natural products with potentially enhanced bioactivities (8,20,21).…”

mentioning

confidence: 99%

De novo production of the plant-derived alkaloid strictosidine in yeast

Brown

Clastre

Courdavault

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

391

347

View full text Add to dashboard Cite

The monoterpene indole alkaloids are a large group of plant-derived specialized metabolites, many of which have valuable pharmaceutical or biological activity. There are ∼3,000 monoterpene indole alkaloids produced by thousands of plant species in numerous families. The diverse chemical structures found in this metabolite class originate from strictosidine, which is the last common biosynthetic intermediate for all monoterpene indole alkaloid enzymatic pathways. Reconstitution of biosynthetic pathways in a heterologous host is a promising strategy for rapid and inexpensive production of complex molecules that are found in plants. Here, we demonstrate how strictosidine can be produced de novo in a Saccharomyces cerevisiae host from 14 known monoterpene indole alkaloid pathway genes, along with an additional seven genes and three gene deletions that enhance secondary metabolism. This system provides an important resource for developing the production of more complex plantderived alkaloids, engineering of nonnatural derivatives, identification of bottlenecks in monoterpene indole alkaloid biosynthesis, and discovery of new pathway genes in a convenient yeast host.

show abstract

Metabolic engineering of Saccharomyces cerevisiae for production of ginsenosides

Cited by 209 publications

References 64 publications

Production of bioactive ginsenosides Rh2 and Rg3 by metabolically engineered yeasts

Production of bioactive ginsenosides Rh2 and Rg3 by metabolically engineered yeasts

Reconstructing the chemical diversity of labdane-type diterpene biosynthesis in yeast

De novo production of the plant-derived alkaloid strictosidine in yeast

Contact Info

Product

Resources

About