Regulation and Evolution of the Malonate and Propionate 1 Catabolism in the Proteobacteria

18 Bacteria catabolize malonate via two pathways, encoded by the mdc and mat genes. In 19 various bacteria, transcription of these genes is controlled by the GntR-family transcription 20 factors MatR/MdcY or/and a LysR-family transcription factor MdcR. Propionate is metabolised 21 via the methylcitrate pathway comprising enzymes encoded by the prp and acn genes. PrpR, the 22 Fis-family sigma54-dependent transcription factor, is known to be a transcriptional activator of 23 the prp genes. Here, we report a detailed comparative genomic analysis of the malonate and 24 propionate metabolism and its regulation in the Proteobacteria. We characterize genomic loci 25 and gene regulation, identify binding motifs for four new TFs, and also new regulon members, in 26 particular, TRAP transporters. We describe restructuring of the genomic loci and regulatory 27 interactions during the evolution of the Proteobacteria. 28