Regulating vitamin B12 biosynthesis via the cbiMCbl riboswitch in Propionibacterium strain UF1

Vitamin B12 (VB12) is a critical micronutrient that controls DNA metabolic pathways to maintain the host genomic stability and tissue homeostasis. We recently reported that the newly discovered commensal Propionibacterium, P. UF1, regulates the intestinal immunity to resist pathogen infection, which may be attributed in part to VB12 produced by this bacterium. Here we demonstrate that VB12 synthesized by P. UF1 is highly dependent on cobA gene-encoding uroporphyrinogen III methyltransferase, and that this vitamin distinctively regulates the cobA operon through its 5′ untranslated region (5′ UTR). Furthermore, conserved secondary structure and mutagenesis analyses revealed a VB12-riboswitch, cbiMCbl (140 bp), within the 5′ UTR that controls the expression of downstream genes. Intriguingly, ablation of the cbiMCbl significantly dysregulates the biosynthesis of VB12, illuminating the significance of this riboswitch for bacterial VB12 biosynthesis. Collectively, our finding is an in-depth report underscoring the regulation of VB12 within the beneficial P. UF1 bacterium, through which the commensal metabolic network may improve gut bacterial cross-feeding and human health.