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Biotechnology letters

Improved campesterol production in engineered Yarrowia lipolytica strains.


PMID 28357621

Abstract

To engineer Yarrowia lipolytica for improving the heterologous production of campesterol (a key precursor to manufacture pharmaceutical steroids). By screening 7-dehydrocholesterol reductase (DHCR7) from diverse species, DHCR7 from Danio rerio was the best candidate for campesterol synthesis. Overexpression of ACL (ATP: citrate lyase) or POX2 (peroxisome acyl-CoA oxidase 2) were key to improving campesterol production. The highest yield of campesterol was 942 mg/l was with the strain overexpressing POX2 in a 5 l bioreactor via high cell density fermentation process with a restricted supply of carbon sourc, sunflower seed oil. A promising platform to synthesize downstream steroid drugs was established. Efficient approaches were provided to improve the production of desired molecules in Y. lipolytica with high oil utilization efficiency.

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C5157
Campesterol, ~65%
C28H48O