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. 2003 Jul;69(7):3924-31.
doi: 10.1128/AEM.69.7.3924-3931.2003.

Regio- and stereoselective metabolism of 7,12-dimethylbenz[a]anthracene by Mycobacterium vanbaalenii PYR-1

Joanna D Moody  1 , Peter P Fu, James P Freeman, Carl E Cerniglia
Affiliations

Regio- and stereoselective metabolism of 7,12-dimethylbenz[a]anthracene by Mycobacterium vanbaalenii PYR-1

Joanna D Moody et al. Appl Environ Microbiol. 2003 Jul.

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.

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Figures

FIG. 1.
FIG. 1.
Reversed-phase HPLC chromatogram showing DMBA and the metabolites formed by M. vanbaalenii PYR-1. The positions of compounds I to V are shown.
FIG. 2.
FIG. 2.
Electron ionization mass spectra of DMBA trans-5,6-dihydrodiol (A) and DMBA cis-5,6-dihydrodiol (B).
FIG. 3.
FIG. 3.
Proton NMR spectra of DMBA trans-5,6-dihydrodiol (A) and DMBA cis-5,6-dihydrodiol (B).
FIG. 4.
FIG. 4.
CD spectra of the two enantiomers of synthetically prepared racemic DMBA trans-5,6-dihydrodiol (— and –––) and DMBA trans-5,6-dihydrodiol from M. vanbaalenii PYR-1 (----) (A) and synthetically prepared racemic DMBA cis-5,6-dihydrodiol (— and –––) and DMBA cis-5,6-dihydrodiol from M. vanbaalenii PYR-1 (----) (B).
FIG. 5.
FIG. 5.
Proposed pathway for the transformation of DMBA by M. vanbaalenii PYR-1.
See this image and copyright information in PMC

References

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