Production of (-)-α-bisabolol in metabolically engineered Saccharomyces cerevisiae

Abstract

(-)-α-Bisabolol is a natural monocyclic sesquiterpene alcohol present in German chamomile and has been used as an ingredient of functional foods, cosmetics and pharmaceuticals. In this study, metabolic engineering strategies were attempted to produce (-)-α-bisabolol in Saccharomyces cerevisiae. The codon-optimized MrBBS gene coding for (-)-α-bisabolol synthase from Matricaria recutita was expressed in S. cerevisiae for (-)-α-bisabolol production. The resulting strain (DM) produced 9.5 mg/L of (-)-α-bisabolol in 24 h of batch culture. Additionally, the mevalonate pathway was intensified by introducing a truncated HMG1 gene coding for HMG-CoA reductase and ERG10 encoding acetyl-CoA thiolase. The resulting strain (DtEM) produced a 2.9-fold increased concentration of (-)-α-bisabolol than the DM strain. To increase the acetyl-CoA pool, the ACS1 gene coding for acetyl-CoA synthetase was also overexpressed in the DtEM strain. Finally, the DtEMA strain produced 124 mg/L of (-)-α-bisabolol with 2.7 mg/L-h of productivity in a fed-batch fermentation, which were 13 and 6.8 times higher than the DM strain in batch culture, respectively. Conclusively, these metabolically-engineered approaches might pave the way for the sustainable production of other sesquiterpenes in engineered S. cerevisiae.

Keywords: (−)-α-Bisabolol; ACS1; ERG10; MrBBS; Saccharomyces cerevisiae; tHMG.