Stereoselective fungal metabolism of 7,12-dimethylbenz[a]anthracene

identification and enantiomeric resolution of a K-region dihydrodiol.

David C McMillan, P. P. Fu, C. E. Cerniglia

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Syncephalastrum racemosum UT-70 and Cunninghamella elegans ATCC 36112 metabolized 7,12-dimethylbenz[a]anthracene (7,12-DMBA) to hydroxymethyl metabolites as well as 7-hydroxymethyl-12-methylbenz[a]anthracene trans-3,4-, -5,6-, -8,9-, and -10,11-dihydrodiols. The 7,12-DMBA metabolites were isolated by reversed-phase high-performance liquid chromatography and identified by their UV-visible absorption, mass, and nuclear magnetic resonance spectral characteristics. A comparison of the circular dichroism spectra of the K-region (5,6-position) dihydrodiol of both fungal strains with those of the 7,12-DMBA 5S,6S-dihydrodiol formed from 7,12-DMBA by rat liver microsomes indicated that the major enantiomer of the 7-hydroxymethyl-12-methylbenz[a]anthracene trans-5,6-dihydrodiol formed by both fungal strains had a 5R,6R absolute stereochemistry. Direct resolution of the fungal trans-5,6-dihydrodiols by chiral stationary-phase high-performance liquid chromatography indicated that the ratios of the R,R and S,S enantiomers were 88:12 and 77:23 for S. racemosum and C. elegans, respectively. These results indicate that the fungal metabolism of 7,12-DMBA at the K region (5,6-position) is highly stereoselective and different from that reported for mammalian enzyme systems.

Original languageEnglish (US)
Pages (from-to)2560-2566
Number of pages7
JournalApplied and environmental microbiology
Volume53
Issue number10
StatePublished - Jan 1 1987

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liquid chromatography
metabolite
metabolism
Syncephalastrum racemosum
Cunninghamella elegans
nuclear magnetic resonance
Cunninghamella
High Pressure Liquid Chromatography
enzyme
enantiomers
Liver Microsomes
Reverse-Phase Chromatography
Circular Dichroism
Magnetic Resonance Spectroscopy
metabolites
circular dichroism spectroscopy
liver microsomes
stereochemistry
reversed-phase high performance liquid chromatography
anthracenes

ASJC Scopus subject areas

  • Biotechnology
  • Food Science
  • Applied Microbiology and Biotechnology
  • Ecology

Cite this

Stereoselective fungal metabolism of 7,12-dimethylbenz[a]anthracene : identification and enantiomeric resolution of a K-region dihydrodiol. / McMillan, David C; Fu, P. P.; Cerniglia, C. E.

In: Applied and environmental microbiology, Vol. 53, No. 10, 01.01.1987, p. 2560-2566.

Research output: Contribution to journalArticle

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abstract = "Syncephalastrum racemosum UT-70 and Cunninghamella elegans ATCC 36112 metabolized 7,12-dimethylbenz[a]anthracene (7,12-DMBA) to hydroxymethyl metabolites as well as 7-hydroxymethyl-12-methylbenz[a]anthracene trans-3,4-, -5,6-, -8,9-, and -10,11-dihydrodiols. The 7,12-DMBA metabolites were isolated by reversed-phase high-performance liquid chromatography and identified by their UV-visible absorption, mass, and nuclear magnetic resonance spectral characteristics. A comparison of the circular dichroism spectra of the K-region (5,6-position) dihydrodiol of both fungal strains with those of the 7,12-DMBA 5S,6S-dihydrodiol formed from 7,12-DMBA by rat liver microsomes indicated that the major enantiomer of the 7-hydroxymethyl-12-methylbenz[a]anthracene trans-5,6-dihydrodiol formed by both fungal strains had a 5R,6R absolute stereochemistry. Direct resolution of the fungal trans-5,6-dihydrodiols by chiral stationary-phase high-performance liquid chromatography indicated that the ratios of the R,R and S,S enantiomers were 88:12 and 77:23 for S. racemosum and C. elegans, respectively. These results indicate that the fungal metabolism of 7,12-DMBA at the K region (5,6-position) is highly stereoselective and different from that reported for mammalian enzyme systems.",
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