Carotenoid-based phenotypic screen of the yeast deletion collection reveals new genes with roles in isoprenoid production

Beside their essential cellular functions, isoprenoids have value as pharmaceuticals, nutriceuticals, pesticides, and fuel alternatives. Engineering microorganisms for production of isoprenoids is relatively easy, sustainable, and cost effective in comparison to chemical synthesis or extraction from natural producers. We introduced genes encoding carotenoid biosynthetic enzymes into the haploid yeast deletion collection to identify gene deletions that improved isoprenoid production. Deletions that showed significant improvement in carotenoid production were further screened for production of bisabolene, an isoprenoid alternative to petroleum-derived diesel. Combining those deletions with other mevalonate pathway modifications increased production of bisabolene from 40 mg/L to 800 mg/L in shake-flask cultures. In a fermentation process, this engineered strain produced 5.2 g/L of bisabolene.

► Yeast deletion collection was screened for improvements in carotenoid production.
► 24 of the highest carotenoid producing strains were tested for bisabolene production.
► Three gene deletions showed enhanced bisabolene production.
► These gene deletions and other modifications increased bisabolene production 20-fold.
► The best producing strain yielded 5.2 g/L of bisabolene in bioreactor experiment.