Biosynthesis of squalene-type triterpenoids in Saccharomyces cerevisiae by expression of CYP505D13 from Ganoderma lucidum

Abstract

Background

Squalene-type triterpenoids (STs) are a class of linearized triterpenoids with significant bioactivities, including anti-cancer, anti-oxidative, and anti-inflammatory activities. The efficient biosynthesis of STs has gained increasing attention.

Results

Using Saccharomyces cerevisiae as a heterologous host, we discovered that overexpression of CYP505D13 from Ganoderma lucidum, a famous medicinal mushroom capable of producing various triterpenoids as secondary metabolites, enables the engineered S. cerevisiae strain to produce two new STs, 4,8-dihydroxy-22,23-oxidosqualene (ST-1), 8-hydroxy-2,3;22,23-squalene dioxide (ST-2), and a known ST, 2,3; 22,23-squalene dioxide (ST-3), at the respective titers of 3.28 mg/L, 13.77 mg/L, and 12.23 mg/L after 59 h fermentation. Furthermore, our in vitro enzymatic assay implies that CYP505D13 is involved in the formation of ST-3.

Conclusions

This study provides a promising alternative to discover STs and facilitate their efficient bioproduction.

Keywords

Cytochrome P450s (CYPs) / Squalene-type triterpenoids (STs) / Saccharomyces cerevisiae / Ganoderma lucidum / Synthetic biology

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Funding

National Natural Science Foundation of China(31600071)

Natural Science Foundation of Shanghai(17ZR1448900)