Production of 13beta-alkyl-3-methoxy-8,14-seco-1,3,5(10),9(11)-gonatetraen-14beta-ol-17-ones and 13beta-alkyl-3-methoxy-8,14-seco-1,3,5(10),9(11)-gonatetraen-17alpha-ol-14-ones by microbial enzymes.
For the purpose of producing hydroxy-keto-seco-steroids in which hydroxyl group is attached to a carbon atom having the R-configuration, numerous biochemically active microorganisms were tested without any success. The hydroxysteroid oxidoreductase enzymes of the investigated bacterial, yeast and fungal strains were suitable only for the production of 17beta-ol-14-one and 14alpha-ol-17-one derivatives. The required compounds were prepared by combinations of enzymatic reactions with chemical reduction. (i) By hydroxysteroid oxidoreductase of Saccharomyces uvarum and Saccharomyces drosophilarum, 17beta-ol-14-one and 14alpha-ol-17-one derivatives of 14,17-dione, respectively, were obtained. (ii) The above compounds were acetylated then reduced by sodium borohydride. (iii) 14beta,17beta-diol-17-acetate and 14alpha,17alpha-diol-14-acetate were dehydrogenated by dehydroxysteroid oxidoreductase of Nocardia sp. and Mycobacterum sp., respectively, in the presence of steroid esterase. The reaction mixture contained either 14beta-ol-17-one or 17alpha-ol-14-one derivatives, since oxidation by hydroxysteroid oxidoreductase was limited to the hydroxyl group attached to a carbon atom having the S-configuration.
D015068:17-Ketosteroids / Q000096:biosynthesis; D001894:Borohydrides; D002474:Cell-Free System; D055598:Chemical Phenomena; D002621:Chemistry; D005417:Flavobacterium / Q000201:enzymology*; D006067:Gonanes / Q000096:biosynthesis*; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D009161:Mycobacterium / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D009615:Nocardia / Q000201:enzymology*; D010084:Oxidation-Reduction; D012440:Saccharomyces / Q000201:enzymology*; D012632:Secosteroids / Q000096:biosynthesis
D015068:17-Ketosteroids; D001894:Borohydrides; D006067:Gonanes; D012632:Secosteroids; D009243:NAD; D006913:Hydroxysteroid Dehydrogenases