Microbial transformation of steroids: contribution to 14 alpha-hydroxylations.
The regioselective and stereoselective hydroxylation of steroids by fungal strains previously known for their hydroxylation capabilities, such as Thamnostylum (= Helicostylum) piriforme ATCC 8992, Mucor griseocyanus ATCC 1207a, Actinomucor elegans (= Mucor parasiticus) MMP 3122 (Mucorales), and Zygodesmus sp. ATCC 14716, was investigated with special interest for the 14 alpha-hydroxylation reaction. A preliminary screening had shown that some of these microorganisms were adequate for the production of 14 alpha-hydroxylated derivatives of the following steroids: progesterone, 5 beta-pregnane-3,20-dione, 3 beta-hydroxy-5 beta-pregnane-20-one, 3 beta-hydroxy-5 beta-17 (alpha H)-etianic acid methyl ester, androst-4-ene-3,17-dione, and testosterone. About 20 metabolites have been isolated and purified by silicagel chromatography and semi-preparative reverse-phase HPLC. These metabolites have been fully characterized by 1H, 13C NMR and mass spectrometry. All the identified metabolites were hydroxylated at some distinct positions, such as 6 beta-, 7 alpha-, 9 alpha-, 14 alpha-, 15 beta-, or dihydroxylated at 6 beta,14 alpha-,7 alpha,14 alpha-, 9 alpha,14 alpha-, 14 alpha,15 alpha-, 14 alpha,15 beta-positions; nine of these metabolites have not been reported previously. The relationship between the structural features of the investigated steroids and the site-specific hydroxylation has been delineated, and progesterone was found to be the best substrate for the production of 14 alpha-hydroxylated derivative, using T. piriforme.
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Unité associée au CNRS N degrees 400, Université René Descartes, Paris, France.
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D000738:Androsterone / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D001230:Aspergillus / Q000378:metabolism; D001711:Biotransformation; D005658:Fungi / Q000378:metabolism*; D005670:Fusarium / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000737:chemistry / Q000378:metabolism*; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D003904:Mitosporic Fungi / Q000378:metabolism; D011374:Progesterone / Q000737:chemistry / Q000378:metabolism; D012233:Rhizopus / Q000378:metabolism; D013256:Steroids / Q000737:chemistry / Q000378:metabolism*; D013739:Testosterone / Q000737:chemistry / Q000378:metabolism
D012739:Gonadal Steroid Hormones; D013256:Steroids; D013739:Testosterone; D011374:Progesterone; D000738:Androsterone