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Rapid oxidation of ring methyl groups is the primary mechanism of biotransformation of gemfibrozil by the fungus Cunninghamella elegans.
Arch Microbiol. 2009 Jun; 191(6):509-17.AM

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.

Authors+Show Affiliations

International Environmental Research Center, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19404612

Citation

Kang, Su-Il, et al. "Rapid Oxidation of Ring Methyl Groups Is the Primary Mechanism of Biotransformation of Gemfibrozil By the Fungus Cunninghamella Elegans." Archives of Microbiology, vol. 191, no. 6, 2009, pp. 509-17.
Kang SI, Kang SY, Kanaly RA, et al. Rapid oxidation of ring methyl groups is the primary mechanism of biotransformation of gemfibrozil by the fungus Cunninghamella elegans. Arch Microbiol. 2009;191(6):509-17.
Kang, S. I., Kang, S. Y., Kanaly, R. A., Lee, E., Lim, Y., & Hur, H. G. (2009). Rapid oxidation of ring methyl groups is the primary mechanism of biotransformation of gemfibrozil by the fungus Cunninghamella elegans. Archives of Microbiology, 191(6), 509-17. https://doi.org/10.1007/s00203-009-0480-0
Kang SI, et al. Rapid Oxidation of Ring Methyl Groups Is the Primary Mechanism of Biotransformation of Gemfibrozil By the Fungus Cunninghamella Elegans. Arch Microbiol. 2009;191(6):509-17. PubMed PMID: 19404612.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapid oxidation of ring methyl groups is the primary mechanism of biotransformation of gemfibrozil by the fungus Cunninghamella elegans. AU - Kang,Su-Il, AU - Kang,Seo-Young, AU - Kanaly,Robert A, AU - Lee,Eunjung, AU - Lim,Yoongho, AU - Hur,Hor-Gil, Y1 - 2009/04/30/ PY - 2009/02/01/received PY - 2009/04/14/accepted PY - 2009/04/08/revised PY - 2009/5/1/entrez PY - 2009/5/1/pubmed PY - 2009/5/30/medline SP - 509 EP - 17 JF - Archives of microbiology JO - Arch. Microbiol. VL - 191 IS - 6 N2 - 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. SN - 1432-072X UR - https://www.unboundmedicine.com/medline/citation/19404612/Rapid_oxidation_of_ring_methyl_groups_is_the_primary_mechanism_of_biotransformation_of_gemfibrozil_by_the_fungus_Cunninghamella_elegans_ L2 - https://dx.doi.org/10.1007/s00203-009-0480-0 DB - PRIME DP - Unbound Medicine ER -