Combinatorial metabolic engineering of <i>Saccharomyces cerevisiae</i> for improved production of 7-dehydrocholesterol.

ABSTRACT: 7-Dehydrocholesterol (7-DHC), a key pharmaceutical intermediate in the production of vitamin D₃, has a wide range of applications. To explore fermentative synthesis of 7-DHC, a 7-DHC-producing Saccharomyces cerevisiae strain was constructed by blocking the competitive pathway, eliminating rate-limiting steps, altering global regulation, and pathway compartmentalization. After blocking the competitive pathway by disrupting ERG5 and ERG6 and introducing DHCR24 from Gallus gallus, S. cerevisiae produced 139.72 mg/L (17.04 mg/g dry cell weight, hereafter abbreviated as DCW) 7-DHC. Subsequent alteration of global regulation by deleting ROX1 and overexpressing UPC2-1 increased 7-DHC production to 217.68 mg/L (37.56 mg/g DCW). To remove

SUBMITTER: Gu Y 

PROVIDER: S-EPMC11610951 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature