Self-sufficient biosynthesis of pregnenolone and progesterone in engineered yeast.
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.
Duport
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Centre de Génétique Moléculaire du CNRS, Gif-sur-Yvette, France.
Spagnoli
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Degryse
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Pompon
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D
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
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