Stereoselective fungal metabolism of methylated anthracenes.
The metabolism of 9-methylanthracene (9-MA), 9-hydroxymethylanthracene (9-OHMA), and 9,10-dimethylanthracene (9,10-DMA) by the fungus Cunninghamella elegans ATCC 36112 is described. The metabolites were isolated by high-performance liquid chromatography and characterized by UV-visible, mass, and 1H nuclear magnetic resonance spectral techniques. The compounds 9-MA and 9,10-DMA were metabolized by two pathways, one involving initial hydroxylation of the methyl group(s) and the other involving epoxidation of the 1,2- and 3,4- aromatic double bond positions, followed by enzymatic hydration to form hydroxymethyl trans-dihydrodiols. For 9-MA metabolism, the major metabolites identified were trans-1,2-dihydro-1,2-dihydroxy and trans-3,4-dihydro-3,4-dihydroxy derivatives of 9-MA and 9-OHMA. 9-OHMA was also metabolized to trans-1,2- and 3,4-dihydrodiol derivatives. The absolute configuration and optical purity were determined for each of the trans-dihydrodiols formed by fungal metabolism and compared with previously published circular dichroism spectral data obtained from rat liver microsomal metabolism of 9-MA, 9-OHMA, and 9,10-DMA. Circular dichroism spectral analysis revealed that the major enantiomer for each dihydrodiol was predominantly in the S,S configuration, in contrast to the predominantly R,R configuration of the trans-dihydrodiol formed by mammalian enzyme systems. These results indicate that C. elegans metabolizes methylated anthracenes in a highly stereoselective manner that is different from that reported for rat liver microsomes.
Cerniglia
C E
CE
National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas 72079.
Campbell
W L
WL
Fu
P P
PP
Freeman
J P
JP
Evans
F E
FE
D000818:Animals; D000873:Anthracenes / Q000378:metabolism*; D002942:Circular Dichroism; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D008862:Microsomes, Liver / Q000378:metabolism; D009090:Mucorales / Q000378:metabolism*; D051381:Rats; D013237:Stereoisomerism
D000873:Anthracenes; C049587:9-hydroxymethylanthracene; C046962:9-methylanthracene; C029126:9,10-dimethylanthracene