A novel class of CoA-transferase involved in short-chain fatty acid metabolism in butyrate-producing human colonic bacteria

Abstract

Bacterial butyryl-CoA CoA-transferase activity plays a key role in butyrate formation in the human colon, but the enzyme and corresponding gene responsible for this activity have not previously been identified. A novel CoA-transferase gene is described from the colonic bacterium Roseburia sp. A2-183, with similarity to acetyl-CoA hydrolase as well as 4-hydroxybutyrate CoA-transferase sequences. The gene product, overexpressed in an Escherichia coli lysate, showed activity with butyryl-CoA and to a lesser degree propionyl-CoA in the presence of acetate. Butyrate, propionate, isobutyrate and valerate competed with acetate as the co-substrate. Despite the sequence similarity to 4-hydroxybutyrate CoA-transferases, 4-hydroxybutyrate did not compete with acetate as the co-substrate. Thus the CoA-transferase preferentially uses butyryl-CoA as substrate. Similar genes were identified in other butyrate-producing human gut bacteria from clostridial clusters IV and XIVa, while other candidate CoA-transferases for butyrate formation could not be detected in Roseburia sp. A2-183. This suggests strongly that the newly identified group of CoA-transferases described here plays a key role in butyrate formation in the human colon.

Culture-Independent Analyses of Temporal Variation of the Dominant Fecal Microbiota and Targeted Bacterial Subgroups in Crohn's Disease

“…These two groups of bacteria are significant members of the gut ecosystem and play central roles in maintaining functions that are essential to gut health (2,11). The phylum Bacteroidetes has been shown to contribute to the host's ability to degrade indigestible carbohydrates (2), while the members of the order Clostridiales have been documented as being the main producers of short-chain fatty acids, such as butyrate, in the gut (8). Thus, any changes in these keystone groups may impact on the total bacterial communities' capacity to provide beneficial functions to the host.…”

Whole-Genome Transcription Profiling Reveals Genes Up-Regulated by Growth on Fucose in the Human Gut Bacterium “ Roseburia inulinivorans ”

“…Although a gene encoding a propionyl CoA transferase could not be detected in R. inulinivorans by use of degenerate PCR primers (P. Louis, personal communication), the bacterium does possess a butyryl CoA transferase (27), and the same enzyme in a related Roseburia sp. can use either propionate or butyrate as a cosubstrate (6).…”

Function and Phylogeny of Bacterial Butyryl Coenzyme A:Acetate Transferases and Their Diversity in the Proximal Colon of Swine

“…This transferase is thought to be especially advantageous in the colonic ecosystem due to the high levels of acetate, allowing butyrate producers to take up and use a waste product of other microbes (15). Many studies have suggested that the majority of butyrate production in hindgut fermenters is the product of But enzyme activity, including in swine (13,14,(16)(17)(18). It should be noted that previous work has suggested that not all enzymes capable of But activity are homologous.…”

“…The sequence variation for the but gene family is poorly defined and currently includes closely related transferases that have differing substrate preferences (16,17,20). The FunGene But protein database is a large repository of But-like protein sequences and is an excellent resource; however, it contains But proteins and similar transferases that have distinct substrate specificities.…”