Biocatalytic modifications of pregnenolone by selected filamentous fungi.

A microbial catalysis is an effective tool for steroid structural modifications allowing generating the compounds which may be difficult to obtain by conventional synthetic methods. Selected fungal strains of Ascomycota and Zygomycota divisions (totally, 75) representing different phyla were screened for their activity toward 3β-hydroxypregn-5-ene-20-one (pregnenolone) focusing on the production of 11α-hydroxyprogesterone. Along with the ability to catalyze 7α-, 7β- and 11α-hydroxylation which was revealed for some representatives of Pleosporaceae, Trichocomaceae, Hypocreaceae, Clavicipitaceae, Microascaceae, Cunninghamellaceae, Mucoraceae and Phycomycetaceae families, micromycete strains belonging to Acremonium, Aspergillus, Curvularia, Rhizopus, and Scopulariopsis genera were selected capable of modifying 3β-ol-5-ene- to 3-keto-4-ene moiety, - this reaction being rather uncommon for fungi. The ability to catalyze double hydroxylation of pregnenolone at positions 7β and 11α by some tested micromycetes was revealed for the first time. Sustainable and high-efficient single-stage production of 11α-hydroxyprogesterone (up to 70%) from pregnenolone which was hitherto unreported was reached with the strain of Aspergillus niger VKM F-212 under the optimized conditions. The results demonstrate a highly diverse biocatalytic potential of fungal strains towards pregnenolone, reveal the existence of novel active biocatalysts that can be exploited for the synthesis of high-value hydroxysteroids and expand knowledge on structural modifications of steroid molecules in lower eukaryotes. [ABSTRACT FROM AUTHOR]