Discovery of a Novel Lidocaine Metabolite by Human Liver Microsome and Identification of Microbial Species Which Produces the Same Metabolite
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- Hori Sho
- School of Pharmaceutical Sciences, Osaka University
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- Taniguchi Hikari
- School of Pharmaceutical Sciences, Osaka University
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- Yoshimura Sota
- School of Pharmaceutical Sciences, Osaka University
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- Takeda Kanako
- School of Pharmaceutical Sciences, Osaka University
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- Yamashita Ryusei
- School of Pharmaceutical Sciences, Osaka University
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- Kimishima Atsushi
- School of Pharmaceutical Sciences, Osaka University
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- Harada Kazuo
- School of Pharmaceutical Sciences, Osaka University
Abstract
<p>Preparation of drug metabolites at the milligram scale is essential for determining the structure and toxicity of drug metabolites. However, their preparation using recombinant proteins and human liver microsomes (HLM) is often difficult because of technical and ethical issues. Reproducing human drug metabolism in food-derived microorganisms may be useful for overcoming these challenges. In this study, we identified an unknown metabolite of the anaesthetic drug lidocaine, which is metabolised by HLM. By screening for lidocaine metabolic activity in five types of foods (blue cheese, shiitake mushroom, natto, yoghurt, and dry yeast), we found that bacteria isolated from natto reproduced the lidocaine metabolic reaction that occurs in HLM. A fraction containing the unknown lidocaine metabolite was prepared through mass cultivation of a Bacillus subtilis standard strain, ethyl acetate extraction, open column chromatography, and HPLC purification. We identified the unknown metabolite as 3-(2,6-dimethylphenyl)-1-ethyl-2-methyl-4-imidazolidinone using NMR. Our results showed that food-derived microorganisms can produce large amounts of human drug metabolites via large-scale cultivation. Additionally, food microorganisms that can reproduce drug metabolism in humans can be used to examine drug metabolites at a low cost and without ethical issues.</p>
Journal
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- Chemical and Pharmaceutical Bulletin
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Chemical and Pharmaceutical Bulletin 72 (4), 393-398, 2024-04-19
The Pharmaceutical Society of Japan