SELF-SUFFICIENT BIOSYNTHESIS OF PREGNENOLONE AND PROGESTERONE IN ENGINEERED YEAST

The first two steps of the steroidogenic pathway were reproduced in Sa ccharomyces cerevisiae. Engineering of sterol biosynthesis by disrupti on of the Delta 22-desaturase gene and introduction of the Arabidopsis thaliana Delta 7-reductase activity and coexpression of bovine side c hain cleavage cytochrome P450, adrenodoxin, and adrenodoxin reductase, lead to pregnenolone biosynthesis from a simple carbon source. Follow ing additional coexpression of human 3 beta-hydroxysteroid dehydrogena se/isomerase, pregnenolone is further metabolized to progesterone. Ste roid formation appears to be coupled to yeast sterol biosynthesis.