New Electron-Transfer Chain to a Flavodiiron Protein in Couples Butyryl-CoA Oxidation to O Reduction.

, a Gram-negative obligate anaerobe, is common to the oral microbiota, but the species is known to infect other sites of the body where it is associated with a range of pathologies. At present, little is known about the mechanisms by which mitigates against oxidative and nitrosative stress. Inspection of the subsp. ATCC 10953 genome reveals that it encodes a flavodiiron protein (FDP; FNP2073) that is known in other organisms to reduce NO to NO and/or O to HO. FNP2073 is dicistronic with a gene encoding a multicomponent enzyme termed BCR for utyryl-oA eductase. BCR is composed of a butyryl-CoA dehydrogenase domain (BCD), the C-terminal domain of the α-subunit of the electron-transfer flavoprotein (Etfα), and a rubredoxin domain. We show that BCR and the FDP form an αβ heterotetramic complex and use butyryl-CoA to selectively reduce O to HO. The FAD associated with the Etfα domain (α-FAD) forms red anionic semiquinone (FAD), whereas the FAD present in the BCD domain (δ-FAD) forms the blue-neutral semiquinone (FADH), indicating that both cofactors participate in one-electron transfers. This was confirmed in stopped-flow studies where the reduction of oxidized BCR with an excess of butyryl-CoA resulted in rapid (<1.6 ms) interflavin electron transfer evidenced by the formation of the FAD. Analysis of bacterial genomes revealed that the dicistron is present in obligate anaerobic gut bacteria considered to be beneficial by virtue of their ability to produce butyrate. Thus, BCR-FDP may help to maintain anaerobiosis in the colon.