Regulation and evolution of the malonate and propionate catabolism in the proteobacteria

Bacteria catabolize malonate via two pathways, encoded by themdc andmat genes. In various bacteria, transcription of these genes is controlled by the GntR family transcription factors (TFs) MatR/MdcY and/or the LysR family transcription factor MdcR. Propionate is metabolized via the methylcitrate pathway, comprising enzymes encoded by the prp and acn genes. PrpR, the Fis family sigma 54-dependent transcription factor, is known to be a transcriptional activator of the prp genes. Here, we re-port a detailed comparative genomic analysis of malonate and propionate metabolism and its regulation in proteobacteria. We characterize genomic loci and gene regulation and identify binding motifs for four new TFs and also new regulonmembers, in particular, tripartite ATP-independent periplasmic (TRAP) transporters. We describe restructuring of the genomic loci and reg-ulatory interactions during the evolution of proteobacteria. Malonate can be used as a carbon source by a variety of bacte-ria, such as Acinetobacter calcoaceticus, Klebsiella pneu-moniae, Pseudomonas fluorescens, and Pseudomonas putida (15). It is a competitive inhibitor of succinate dehydrogenase. Malonate was found in symbiotic legumes and in developing rat brains (15, 16). Malonate metabolism is essential in symbiotic nitrogen me-tabolism, since mutant bacteria with deleted malonate metabolic genes lose this symbiosis ability (13). In addition, malonate met-abolic genes have been used for generation of the industrial strain of Streptomyces for the production of antibiotics (13). Two groups of structural genes involved in malonate me-tabolism have been characterized. The first group was de-scribed for Rhizobium leguminosarum (16). It comprises three clustered malonate metabolic genes, matA, matB, and matC, and the divergently transcribed gene of the malonate regulator matR (Table 1). The MatR transcription factor (TF) belongs to the FadR subfamily of the GntR family. Another system for malonate metabolism was described fo