Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota

Yijun Zhu; Eleanor Jameson; Marialuisa CrosattiHendrik Sch?ferKumar RajakumarTimothy D. H. BuggYin Chen

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Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota

机译：Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota

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Dietary intake of L-carnitine can promote cardiovascular diseases in humans through microbial production of trimethylamine (TMA) and its subsequent oxidation to trimethylamine N-oxide by hepatic flavin-containing monooxygenases. Although our microbiota are responsible for TMA formation from carnitine, the underpinning molecular and biochemical mechanisms remain unclear. In this study, using bioinformatics approaches, we first identified a two-component Rieske-type oxygenase/reductase (CntAB) and associated gene cluster proposed to be involved in carnitine metabolism in representative genomes of the human microbiota. CntA belongs to a group of previously uncharacterized Rieske-type proteins and has an unusual “bridging” glutamate but not the aspartate residue, which is believed to facilitate intersubunit electron transfer between the Rieske center and the catalytic mononuclear iron center. Using Acinetobacter baumannii as the model, we then demonstrate that cntAB is essential in carnitine degradation to TMA. Heterologous overexpression of cntAB enables Escherichia coli to produce TMA, confirming that these genes are sufficient in TMA formation. Site-directed mutagenesis experiments have confirmed that this unusual “bridging glutamate” residue in CntA is essential in catalysis and neither mutant (E205D, E205A) is able to produce TMA. Taken together, the data in our study reveal the molecular and biochemical mechanisms underpinning carnitine metabolism to TMA in human microbiota and assign the role of this novel group of Rieske-type proteins in microbial carnitine metabolism.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2014年第11期|4268-4273|共6页
作者
Yijun Zhu; Eleanor Jameson; Marialuisa CrosattiHendrik Sch?ferKumar RajakumarTimothy D. H. BuggYin Chen;
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作者单位

School of Life Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom;

Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom;

Department of Chemistry, University of Warwick, Coventry CV4 7AL, United Kingdom;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Carnitine; metabolism; trimethylamine;

Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota

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