Regio- and Stereoselective Metabolism of 7,12-Dimethylbenz[ a ]anthracene by Mycobacterium vanbaalenii PYR-1

Abstract

ABSTRACT The degradation of 7,12-dimethylbenz[ a ]anthracene (DMBA), a carcinogenic polycyclic aromatic hydrocarbon, by cultures of Mycobacterium vanbaalenii PYR-1 was studied. When M. vanbaalenii PYR-1 was grown in the presence of DMBA for 136 h, high-pressure liquid chromatography (HPLC) analysis showed the presence of four ethyl acetate-extractable compounds and unutilized substrate. Characterization of the metabolites by mass and nuclear magnetic resonance spectrometry indicated initial attack at the C-5 and C-6 positions and on the methyl group attached to C-7 of DMBA. The metabolites were identified as cis -5,6-dihydro-5,6-dihydroxy-7,12-dimethylbenz[ a ]anthracene (DMBA cis -5,6-dihydrodiol), trans -5,6-dihydro-5,6-dihydroxy-7,12-dimethylbenz[ a ]anthracene (DMBA trans -5,6-dihydrodiol), and 7-hydroxymethyl-12-methylbenz[ a ]anthracene, suggesting dioxygenation and monooxygenation reactions. Chiral stationary-phase HPLC analysis of the dihydrodiols showed that DMBA cis -5,6-dihydrodiol had 95% 5 S ,6 R and 5% 5 R ,6 S absolute stereochemistry. On the other hand, the DMBA trans -5,6-dihydrodiol was a 100% 5 S ,6 S enantiomer. A minor photooxidation product, 7,12-epidioxy-7,12-dimethylbenz[ a ]anthracene, was also formed. The results demonstrate that M. vanbaalenii PYR-1 is highly regio- and stereoselective in the degradation of DMBA.