Bacterial Cysteate Dissimilatory Pathway Involves a Racemase and D-cysteate Sulfo-Lyase

The sulfite-reducing bacterium Bilophila wadsworthia, a common human intestinal pathobiont, is unique in its ability to metabolize a wide variety of sulfonates to generate sulfite as a terminal electron acceptor (TEA). The resulting formation of H2S is implicated in inflammation and colon cancer. L-cysteate, an oxidation product of L-cysteine, is among the sulfonates metabolized by B. wadsworthia, although the enzymes involved remain unknown. Here we report a pathway for L-cysteate dissimilation in B. wadsworthia RZATAU, involving isomerization of L-cysteate to n-cysteate by a cysteate racemase (BwCuyB), followed by cleavage into pyruvate, ammonia and sulfite by a n-cysteate sulfo-lyase (BwCuyA). The strong selectivity of BwCuyA for n-cysteate over L-cysteate was rationalized by protein structural modeling. A homolog of BwCuyA in the previously reported to be a L-cysteate sulfo-lyase, but our experiments confirm that SpCuyA too displays a strong selectivity for n-cysteate. Growth of B. wadsworthia with cysteate as the electron acceptor is accompanied by production of H2S and induction of BwCuyA. Close homologs of BwCuyA and BwCuyB are present in diverse bacteria, including many sulfate- and sulfite-reducing bacteria, suggesting their involvement in cysteate degradation in different biological environments.