Rapid oxidation of ring methyl groups is the primary mechanism of biotransformation of gemfibrozil by the fungus <Emphasis Type="Italic">Cunninghamella elegans</Emphasis> |
| |
Authors: | Su-Il Kang Seo-Young Kang Robert A Kanaly Eunjung Lee Yoongho Lim Hor-Gil Hur |
| |
Institution: | (1) International Environmental Research Center, Gwangju Institute of Science and Technology, Gwangju, 500-712, Republic of Korea;(2) Department of Genome Systems, Faculty of Bionanoscience, Yokohama City University, Yokohama 236-002, Japan;(3) Department of Bioscience and Biotechnology, and Bio/Molecular Informatics Center, Konkuk University, Seoul, 143-701, Republic of Korea;(4) Department of Environmental Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, 500-712, Republic of Korea; |
| |
Abstract: | The hypolipidemic agent gemfibrozil (GEM), which has been studied for its metabolism in humans and animals, was investigated
to elucidate its primary metabolism by Cunninghamella elegans. The fungus produced ten metabolites (FM1–FM9 and FM6′) from the biotransformation of GEM. Based on LC/MS/MS and NMR analyses,
a major metabolite, FM7, was identified as 2′-hydroxymethyl GEM. FM6 was considered to be 5′-hydroxymethyl GEM, after comparison
of results LC/MS, LC/MS/MS, and UV absorption spectra to FM7. The combined concentration of FM6 and FM7 was found to increase
up to 0.83 mM by day 2, and then decreased gradually with incubation time, followed by a noticeable increase in the biotransformation
product, FM1, up to 0.86 mM by day 15. NMR analyses confirmed that FM1 was 2′,5′-dihydroxymethyl GEM. Further minor oxidations
of the aromatic ring and carboxylic acid intermediates were also detected. Based upon these findings, the major fungal metabolic
pathway for GEM is likely to occur via production of 2′,5′-dihydroxymethyl GEM from 2′-hydroxymethyl GEM. These relatively
rapid and diverse biotransformations of GEM by C. elegans suggest that depending upon conditions, it may also follow a similar biodegradation fate when released into the natural environment. |
| |
Keywords: | Cunninghamella elegans Fungal metabolism Gemfibrozil Hydroxylation Hypolipidemic |
本文献已被 SpringerLink 等数据库收录! |
|