[11beta-Hydroxylation of 6alpha-Fluoro-16alpha-Methyl-Deoxycorticosterone 21-Acetate by filamentous fungi].

Abstract

Selected filamentous fungi--98 strains of 31 genera--were screened for the ability to catalyze 11beta-hydroxylation of 6alpha-fluoro-16alpha-methyl-deoxycorticosterone 21-acetate (FM-DCA). It was established that representatives of the genera Gongronella, Scopulariopsis, Epicoccum, and Curvularia have the ability to activate 11beta-hydroxylase steroids. The strains of Curvularia lunata VKM F-644 and Gongronella butleri VKM F-1033 expressed maximal activity and formed 6lpha-fluoro-16alpha-methyl-corticosterone as a major bioconversion product from FM-DCA. The structures of the major products and intermediates of the bioconversion were confirmed by TLC, H PLC, MS and 1H NMR analyses. Different pathways of 6alpha-fluoro-16alpha-methyl-corticosterone formation by C. lunata and G. butleri strains were proposed based on intermediate identification. The constitutive character and membrane-binding localization were evidence of a 11beta-hydroxylating system in G. butleri, while an inducible character and microsomal localization was confirmed for 11beta-hydroxylase of C. lunata. Under optimized conditions, the molar yield of 6alpha-fluoro-16alpha-methyl-corticosterone reached 65% at a FM-DCA substrate loading of 6 g/L.