气候变化领域集成服务门户(CCPortal): Elucidation of an anaerobic pathway for metabolism of L-carnitine-derived γ-butyrobetaine to trimethylamine in human gut bacteria

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DOI	10.1073/pnas.2101498118
	Elucidation of an anaerobic pathway for metabolism of L-carnitine-derived γ-butyrobetaine to trimethylamine in human gut bacteria
	Rajakovich L.J.; Fu B.; Bollenbach M.; Balskus E.P.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:32
英文摘要	Trimethylamine (TMA) is an important gut microbial metabolite strongly associated with human disease. There are prominent gaps in our understanding of how TMA is produced from the essential dietary nutrient L-carnitine, particularly in the anoxic environment of the human gut where oxygen-dependent L-carnitine-metabolizing enzymes are likely inactive. Here, we elucidate the chemical and genetic basis for anaerobic TMA generation from the L-carnitine-derived metabolite γ-butyrobetaine (γbb) by the human gut bacterium Emergencia timonensis. We identify a set of genes up-regulated by γbb and demonstrate that the enzymes encoded by the induced γbb utilization (bbu) gene cluster convert γbb to TMA. The key TMAgenerating step is catalyzed by a previously unknown type of TMAlyase enzyme that utilizes a putative flavin cofactor to catalyze a redox-neutral transformation. We identify additional cultured and uncultured host-associated bacteria that possess the bbu gene cluster, providing insights into the distribution of anaerobic γbb metabolism. Lastly, we present genetic, transcriptional, and metabolomic evidence that confirms the relevance of this metabolic pathway in the human gut microbiota. These analyses indicate that the anaerobic pathway is a more substantial contributor to TMA generation from L-carnitine in the human gut than the previously proposed aerobic pathway. The discovery and characterization of the bbu pathway provides the critical missing link in anaerobic metabolism of L-carnitine to TMA, enabling investigation into the connection between this microbial function and human disease. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	L-carnitine; Microbiota; Trimethylamine
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238441
作者单位	Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, United States
推荐引用方式 GB/T 7714	Rajakovich L.J.,Fu B.,Bollenbach M.,et al. Elucidation of an anaerobic pathway for metabolism of L-carnitine-derived γ-butyrobetaine to trimethylamine in human gut bacteria[J],2021,118(32).
APA	Rajakovich L.J.,Fu B.,Bollenbach M.,&Balskus E.P..(2021).Elucidation of an anaerobic pathway for metabolism of L-carnitine-derived γ-butyrobetaine to trimethylamine in human gut bacteria.Proceedings of the National Academy of Sciences of the United States of America,118(32).
MLA	Rajakovich L.J.,et al."Elucidation of an anaerobic pathway for metabolism of L-carnitine-derived γ-butyrobetaine to trimethylamine in human gut bacteria".Proceedings of the National Academy of Sciences of the United States of America 118.32(2021).