Elucidation of an anaerobic pathway for metabolism of <scp>l</scp> -carnitine–derived γ-butyrobetaine to trimethylamine in human gut bacteria
Lauren J. Rajakovich, Beverly Fu, Maud Bollenbach, Emily P. Balskus
Abstract
Significance Trimethylamine (TMA) is a disease-associated metabolite produced in the human body exclusively by microbes. Gut microbes generate TMA from essential nutrients consumed in the human diet, including l -carnitine. However, our understanding of the biochemical mechanisms involved in these transformations is incomplete. In this work, we define the biochemical pathway and genetic components in gut bacteria required for anaerobic production of TMA from γ-butyrobetaine, a metabolite derived from l -carnitine. This discovery identifies a new type of TMA-producing enzyme and fills a critical gap in our knowledge of l -carnitine metabolism to TMA in the anaerobic environment of the human gut. This knowledge will enable evaluation of the link between l -carnitine metabolism and human disease and the design of potential therapeutics.