Vitamin B12 partners the CarH repressor to downregulate a photoinducible promoter in Myxococcus xanthus

A light-inducible promoter, P-B, drives expression of the carB operon in Myxococcus xanthus. Repressed by CarA in the dark, PB is activated when CarS, produced in the light, sequesters CarA to prevent operator-CarA binding. The MerR-type, N-terminal domain of CarA, which mediates interactions with both operator and CarS, is linked to a C-terminal oligomerization module with a predicted cobalamin-binding motif. Here, we show that although CarA does bind vitamin B-12, mutating the motif involved has no effect on its ability to repress PB. Intriguingly, PB could be repressed in the dark even with no CarA, so long as B-12 and an intact CarA operator were present. We have discovered that this effect of B-12 depends on the gene immediately downstream of carA. Its product, CarH, also consists of a MerR-type, N-terminal domain that specifically recognizes the CarA operator and CarS, linked to a predicted B-12-binding C-terminal oligomerization module. The B-12-mediated repression of PB in the dark is relieved by deleting carH, by mutating the DNA- or B-12-binding residues of CarH, or by illumination. Our findings unveil parallel regulatory circuits that control a light-inducible promoter using a transcriptional factor repertoire that includes a paralogous gene pair and vitamin B-12.