Microbial synthesis of 1 beta- and 15 beta-hydroxylated bile acids.

Lithocholic, deoxycholic, and cholic acids were incubated with the molds Absidia coerulea Bain (CBS 105.08, I), three strains of Rhizoctonia solani Kühn (CBS 130.14 (II), CBS 341.36 (III), CBS 325.47 (IV)), and Penicillium species ATCC 12556 (V). The products were analyzed by gas-liquid chromatography and partially characterized by gas-liquid chromatography-mass spectrometry. Lithocholic acid was most extensively hydroxylated while cholic acid yielded only traces of hydroxylated metabolites. I, II, III, and V hydroxylated at position C-1; I at C-6; I and II at C-7; III at C-12; and I, II, IV, and V at C-15. Hydroxylations at unidentified positions were observed for all molds, and oxidoreductions at C-7 and C-12 were carried out by I, II, and III. The two major trihydroxycholanoates formed by V from deoxycholic acid were characterized by chemical, mass spectrometric, and nuclear magnetic resonance techniques as 1 beta, 3 alpha, 12 alpha- and 3 alpha, 12 alpha, 15 beta-trihydroxy-5 beta-cholanoic acids. The former bile acid was identical with the 1,3,12-trihydroxycholanoic acid present in human urine.