title: Self-sufficient biosynthesis of pregnenolone and progesterone in engineered yeast.
abstract: The first two steps of the steroidogenic pathway were reproduced in Saccharomyces cerevisiae. Engineering of sterol biosynthesis by disruption of the delta 22-desaturase gene and introduction of the Arabidopsis thaliana delta 7-reductase activity and coexpression of bovine side chain cleavage cytochrome P450, adrenodoxin, and adrenodoxin reductase, lead to pregnenolone biosynthesis from a simple carbon source. Following additional coexpression of human 3 beta-hydroxysteroid dehydrogenase/isomerase, pregnenolone is further metabolized to progesterone. Steroid formation appears to be coupled to yeast sterol biosynthesis.
authors.affiliation: Centre de Génétique Moléculaire du CNRS, Gif-sur-Yvette, France.
authors.forename: C
authors.initials: C
authors.lastname: Duport
authors.forename: R
authors.initials: R
authors.lastname: Spagnoli
authors.forename: E
authors.initials: E
authors.lastname: Degryse
authors.forename: D
authors.initials: D
authors.lastname: Pompon
mesh_terms: D000325:Adrenodoxin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017360:Arabidopsis; D002417:Cattle; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D002849:Chromatography, Gas; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D005287:Ferredoxin-NADP Reductase / Q000235:genetics / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D018014:Gene Transfer Techniques; D005818:Genetic Engineering; D006801:Humans; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011284:Pregnenolone / Q000096:biosynthesis*; D011374:Progesterone / Q000096:biosynthesis*; D011375:Progesterone Reductase / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D013251:Steroid Isomerases / Q000235:genetics / Q000378:metabolism
chemical_list: C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D009097:Multienzyme Complexes; D029701:Saccharomyces cerevisiae Proteins; C033144:lathosterol delta-5-dehydrogenase; D000325:Adrenodoxin; D011374:Progesterone; D011284:Pregnenolone; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D011375:Progesterone Reductase; C066577:ERG5 protein, S cerevisiae; D002786:Cholesterol Side-Chain Cleavage Enzyme; D005287:Ferredoxin-NADP Reductase; D044925:Oxidoreductases Acting on CH-CH Group Donors; D013251:Steroid Isomerases; D005690:Galactose