A pathway for D-cysteinolate degradation in sulfate- and sulfite-reducing bacteria

Sulfonates, characterized by a C-SO₃^- moiety, are widespread in the environment. Sulfate- and sulfite-reducing bacteria degrade many naturally occurring sulfonates to produce H₂S, playing a vital role in sulfur metabolism in anaerobic environments, including the human gut. One of the most abundant sulfonates in marine environments is D-cysteinolate, which functions as an osmolyte in many marine organisms, though mechanisms for its anaerobic degradation remain unknown. Here, we identify and characterize a gene cluster encoding a D-cysteinolate degradation pathway, found in sulfate- and sulfite-reducing bacteria from both environmental sources and the human gut. In this pathway, D-cysteinolate is first epimerized by a pyridoxal phosphate (PLP)-dependent cysteinolate racemase and oxidized by L-cysteinolate dehydrogenase to produce L-cysteate. Subsequent degradation by the recently characterized PLP-dependent enzymes cysteate racemase and D-cysteate sulfo-lyase yields ammonia, pyruvate, and sulfite, for further reduction to H₂S. Given the abundance of cysteinolate in marine-derived foods, our study lays the foundation for further exploring its role in H₂S production within the human gut microbiome.