Two global regulatory systems (Crp and Arc) control the cobalamin/propanediol regulon of Salmonella typhimurium.

The genes for cobalamin (vitamin B12) biosynthesis (cob) are coregulated with genes for degradation of propanediol (pdu). Both the cob and pdu operons are induced by propanediol by means of a positive regulatory protein, PocR. This coregulation of a synthetic and a degradative pathway reflects the fact that vitamin B12 is a required cofactor for the first enzyme in propanediol breakdown. The cob/pdu regulon is induced by propanediol under two sets of growth conditions, i.e., during aerobic respiration of a poor carbon source and during anaerobic growth. We provide evidence that, under aerobic conditions, the Crp/cyclic AMP system is needed for all induction of the pocR, cob, and pdu genes. Anaerobically, the Crp/cyclic AMP and ArcA/ArcB systems act additively to support induction of the same three transcription units. The fact that these global control systems affect expression of the gene for the positive regulatory protein (pocR) as well as the pdu and cob operons is consistent with our previous suggestion that these two global controls may act directly only on the pocR gene; their control over the cob and pdu operons may be an indirect consequence of their effect on the level of PocR activator protein. The reported experiments were made possible by the observation that pyruvate supports aerobic growth of all of the mutants tested (cya, crp, arcA, and arcB); pyruvate also supports anaerobic growth of these mutants if the alternative electron acceptor, fumarate, is provided. By using pyruvate as a carbon source, it was possible to grow all of these mutant strains under identical conditions and compare their expression of the cob/pdu regulon. The role of Crp in control of vitamin B12 synthesis suggests that the major role of vitamin B12 in Salmonella spp. is in catabolism of carbon sources; the coregulation of the cob and pdu operons suggests that propanediol is the major vitamin B12-dependent carbon source.