Diverting mevalonate pathway metabolic flux leakage in Saccharomyces cerevisiae for monoterpene geraniol production from cane molasses

Geraniol has versatile applications in the fragrance, pharmacy, and biofuel industries. This monoterpene is produced via the mevalonate pathway in the yeast Saccharomyces cerevisiae. However, carbon flux leakage restricts the efficient biosynthesis of target compounds via this pathway. In this work, the mevalonate pathway of the recombinant S. cerevisiae was reprogrammed by introducing an isopentenyl phosphate kinase (IPK) and to establish an isopentenyl phosphate utilization (IPU) bypass that can utilise the isopentenyl phosphate (IP) produced from phosphomevalonate decarboxylase (PMD). Geraniol production was increased by 225% in the engineered strain. The yield of geraniol was further enhanced to 156.2 ± 6.6 mg/L through optimisation of key rate-limiting enzymes of the mevalonate pathway. Using pretreated molasses as a carbon source yielded 180.9 ± 2.9 mg/L of geraniol under optimal fermentation conditions, the highest reported titre to date using molasses medium. Modification of the mevalonate pathway can provide a commercially feasible strategy for monoterpene synthesis in engineered S. cerevisiae.