Bioconversion of steroids by Cochliobolus lunatus--II. 11 beta-hydroxylation of 17 alpha, 21-dihydroxypregna-1,4-diene-3,20-dione 17-acetate in dependence of the inducer structure.
The 11 beta-hydroxylase of the filamentous fungus Cochliobolus lunatus m 118 was induced with the substrate 17 alpha, 21-dihydroxypregna-1,4-diene-3,20-dione 17-acetate (11 beta-deoxyprednisolone 17-acetate) itself, substrate analogues, different pregnane compounds, sterols, intermediates of microbial sterol side-chain degradation or bile acids, together with 24 different steroids in a standardized test system. The resulting 11 beta-hydroxylation rate, leading to prednisolone 17-acetate and prednisolone, respectively, was determined and compared with the hydroxylation rate of non-induced cultures. The transformation yield strongly depended on the inducer structure. The microbial sterol side-chain degradation intermediates (20S)-20-hydroxymethylpregn-4-en-3-one and the corresponding pregna-1,4-diene compound caused the highest induction effects (induction factors 5.1 and 4.9, respectively). The metabolism of (20S)-20-hydroxymethylpregna-1,4-dien-3-one during the cultivation was elucidated. The induction effect decreased with the rising oxidation of the inducer. The significant increase of the 11 beta-hydroxylation rate of 1-dehydro-pregnane substrates by specific induction allows alternative pathways to glucocorticoid partial syntheses.
Undisz
K
K
Central Institute of Microbiology and Experimental Therapy, Jena, Germany.
Groh
H
H
Stopsack
H
H
Hörhold-Schubert
C
C
D001203:Ascomycota / Q000201:enzymology*; D004790:Enzyme Induction; D006900:Hydroxylation; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D011278:Pregnanes / Q000494:pharmacology; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism*; D013329:Structure-Activity Relationship
D011278:Pregnanes; C077925:17,21-dihydroxypregna-1,4-diene-3,20-dione 17-acetate; D011239:Prednisolone; D013252:Steroid 11-beta-Hydroxylase