Biosynthesis of Valerenic acid by Engineered Saccharomyces cerevisiae

Abstract

Objective To produce valerenic acid (VA) in Saccharomyces cerevisiae by engineering a heterologous synthetic pathway.Result Valerena-4,7(11)-diene synthase (VDS) derived from Valeriana officinalis was expressed in S. cerevisiae to generate valerena-4,7(11)-diene as the precursor of VA. By overexpressing the key genes of mevalonate (MVA) pathway ERG8, ERG12 and ERG19 and integrating 4 copies of MBP (maltose binding protein)-VDS-ERG20 gene expression caskets into genome, the production of valerena-4,7(11)-diene was improved to 75 mg/L. On this basis, VA synthases from Lactuca sativa was expressed to produce VA and the most effective VA production strain was used for fermentation, and the yield of VA reached mg/L in the flask and 6.8 mg/L in a 5-L bioreactor fed glucose and ethanol. Conclusions The heterologous synthesis of VA in S. cerevisiae increases the production of VA and provides a reference method for the biosynthesis of other sesquiterpenes.