Dual feedback inhibition of ATP-dependent caffeate activation economizes ATP in caffeate-dependent electron bifurcation

This study reports a dual feedback inhibition of caffeoyl-CoA synthetase by two downstream products, hydrocaffeate and hydrocaffeoyl-CoA. It elucidates how such dual feedback inhibition suppresses ATP-dependent caffeoyl-CoA synthesis, hence making the ATP-independent route the main pathway of caffeate activation. This newly discovered mechanism contributes to our current understanding of ATP conservation during the caffeate-dependent electron-bifurcating pathway in the ecologically important acetogen <i>Acetobacterium woodii</i>. Bioinformatic mining of microbial genomes revealed contiguous genes homologous to <i>carABC</i> within the genomes of other anaerobes from various environments, suggesting this mechanism may be widely used in other CoA-dependent electron-bifurcating pathways.