title: Regio- and stereoselective metabolism of 7,12-dimethylbenz[a]anthracene by Mycobacterium vanbaalenii PYR-1.
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% 5S,6R and 5% 5R,6S absolute stereochemistry. On the other hand, the DMBA trans-5,6-dihydrodiol was a 100% 5S,6S 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.
authors.affiliation: Division of Microbiology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
authors.forename: Joanna D
authors.initials: JD
authors.lastname: Moody
authors.forename: Peter P
authors.initials: PP
authors.lastname: Fu
authors.forename: James P
authors.initials: JP
authors.lastname: Freeman
authors.forename: Carl E
authors.initials: CE
authors.lastname: Cerniglia
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000737:chemistry* / Q000378:metabolism*; D001673:Biodegradation, Environmental; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009161:Mycobacterium / Q000254:growth & development / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D003470:Culture Media; D015127:9,10-Dimethyl-1,2-benzanthracene