Project description:Eubacterium limosum ATCC 8486 makes acetate and butyrate from various substrates and is found in the human intestine. The proteome of L-carnitine-grown Eubacterium limosum was obtained in order to identify enzymes required for growth on L-carnitine, in particular to identify components that are unique to growth on L-carnitine in comparison to other substrates for acetogenesis, such as lactic acid. L-carnitine and derviatives are converted to trimethylamine (TMA) by certain members of the gut microbiome, metabolism of TMA is now tied to progression of cardiovascular disease. Demethylation of carnitine is observed during growth of Eubacterium limosum on this substrate, and does not produce TMA. Carnitine demethylation by organisms like Eubacterium limosum could lessen TMA production in the gut, thereby lessening the propensity towards atherorsclerosis caused by metabolism of TMA in the body. The carnitine proteome led to the description of a carnitine:tetrahydrofolate methyltransferase system. The key carnitine demethylating enzyme is a member of the widespread TMA methyltransferase protein superfamily.
Project description:Eubacterium limosum ATCC 8486 makes acetate and butyrate from various substrates and is found in the human intestine. The proteome of gamma-butyrobetaine -grown Eubacterium limosum was obtained in order to identify enzymes required for growth on gamma-butyrobetaine, in particular to identify components that are unique to growth on gamma-butyrobetaine in comparison to other substrates for acetogenesis, such as lactic acid, L-carnitine, or proline betaine. Gamma-butyrobetaine is converted to trimethylamine (TMA) by certain members of the gut microbiome. Subsequent liver metabolism of TMA is now tied to progression of cardiovascular disease. Demethylation of gamma-butyrobetaine is observed during growth of Eubacterium limosum on this substrate, and does not produce TMA. Gamma-butyrobetaine demethylation by organisms like Eubacterium limosum could lessen TMA production in the gut, thereby lessening the propensity towards atherosclerosis caused by metabolism of TMA in the body. This proteome led to discovery of gamma-butyrobetaine:tetrahydrofolate methyltransferase system. The key gamma-butyrobetaine demethylating enzyme is a member of the widespread TMA methyltransferase protein superfamily.