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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenodoxin / genetics
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Adrenodoxin / metabolism
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Animals
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Arabidopsis
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Cattle
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Cholesterol Side-Chain Cleavage Enzyme / genetics
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Cholesterol Side-Chain Cleavage Enzyme / metabolism
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Chromatography, Gas
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Cytochrome P-450 Enzyme System / genetics
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Cytochrome P-450 Enzyme System / metabolism
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Ferredoxin-NADP Reductase / genetics
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Ferredoxin-NADP Reductase / metabolism
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Galactose / metabolism
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Gene Transfer Techniques
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Genetic Engineering*
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Humans
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Multienzyme Complexes / genetics
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Multienzyme Complexes / metabolism
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Oxidoreductases / genetics
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Oxidoreductases / metabolism
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Oxidoreductases Acting on CH-CH Group Donors*
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Pregnenolone / biosynthesis*
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Progesterone / biosynthesis*
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Progesterone Reductase / genetics
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Progesterone Reductase / metabolism
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae Proteins
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Steroid Isomerases / genetics
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Steroid Isomerases / metabolism
Substances
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3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase
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Multienzyme Complexes
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Saccharomyces cerevisiae Proteins
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lathosterol delta-5-dehydrogenase
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Adrenodoxin
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Progesterone
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Pregnenolone
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Cytochrome P-450 Enzyme System
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Oxidoreductases
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Progesterone Reductase
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ERG5 protein, S cerevisiae
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Cholesterol Side-Chain Cleavage Enzyme
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Ferredoxin-NADP Reductase
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Oxidoreductases Acting on CH-CH Group Donors
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Steroid Isomerases
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Galactose