Reduction of the 20-carbonyl group of C-21 steroids by spores of Fusarium solani and other microorganisms. I. Side-chain degradation, epoxide cleavage, and substrate specificity.
The spores of Fusarium solani reduced the C(2)-carbonyl group, 1-dehydrogenated ring "A" and cleaved the side chain of 16alpha, 17alpha-oxidopregn-4-ene-3, 20-dione (16alpha, 17alpha-oxidoprogesterone)(I) to give the following products: 20alpha-hydroxy-16alpha, 17alpha-oxidopregn-4-en-3-one(II); 20alpha-hydroxy-16alpha, 17alpha-oxidopregna-1, 4-dien-3-one(III); 16alpha-hydroxy-17a-oxa-androsta-1, 4-diene-3, 17-dione (16alpha-hydroxy-1-dehydrotestololactone)(IV); and 16alpha, 17beta-dihydroxy-androsta-1, 4-dien-3-one (16alpha-hydroxy-1-dehydrotestosterone)(V). When II was used as a substrate, it was metabolized into III, IV, and V at a slower rate than I. Furthermore, 16alpha-hydroxy-androst-4-ene-3, 17-dione (16alpha-hydroxyandrostenedione)(X) was transformed into IV and V. Pregn-4-ene-3, 20-dione (progesterone)(XII) was transformed into androsta-1, 4-diene-3, 17-dione (androstadienedione)(VIII) and 17a-oxa-androsta-1, 4-diene-3, 17-dione (1-dehydrotestololactone)(IX), while 17alpha-hydroxy-pregn-4-ene-3, 20-dione (17alpha-hydroxyprogesterone)(VI) was converted into its 1-dehydro analogue (VII) without accumulation of any 20-dihydro compounds. Substrate specificity in the 20-reductase system of F. solani, Cylindrocarpon radicicola, Septomyxa affinis, Bacillus lentus, and three strains of B. sphaericus are demonstrated. The 20-reductase is active only on steroids having the 16alpha, 17alpha-oxido, and Delta(4)-3-keto functions. Evidence of competition between side-chain degrading enzymes and the 20-reductase for the steroid molecule and evidence of side-chain degradation followed by epoxide cleavage (and not the reverse) are presented. A mechanism for the epoxide opening by nongerminating spores of F. solani is postulated.
D015068:17-Ketosteroids / Q000096:biosynthesis / Q000378:metabolism; D000731:Androstanes / Q000096:biosynthesis / Q000378:metabolism; D001407:Bacillus / Q000378:metabolism; D004988:Ethers, Cyclic / Q000096:biosynthesis / Q000378:metabolism; D005670:Fusarium / Q000201:enzymology / Q000378:metabolism*; D006908:Hydroxyprogesterones / Q000378:metabolism; D006913:Hydroxysteroid Dehydrogenases; D006914:Hydroxysteroids / Q000096:biosynthesis / Q000378:metabolism; D007664:Ketosteroids / Q000096:biosynthesis / Q000378:metabolism; D010088:Oxidoreductases; D011278:Pregnanes / Q000096:biosynthesis / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism; D013045:Species Specificity; D013170:Spores / Q000378:metabolism*; D013172:Spores, Fungal / Q000201:enzymology / Q000378:metabolism; D013329:Structure-Activity Relationship
D015068:17-Ketosteroids; D000731:Androstanes; D004988:Ethers, Cyclic; D006908:Hydroxyprogesterones; D006914:Hydroxysteroids; D007664:Ketosteroids; D011278:Pregnanes; D011374:Progesterone; D010088:Oxidoreductases; D006913:Hydroxysteroid Dehydrogenases