A finely tuned regulatory circuit of the nicotinic acid degradation pathway in Pseudomonas putida

The biochemistry of nicotinic acid (NA) degradation is known but the transcriptional control of the genes involved is still poorly studied. We report here the transcriptional regulatory circuit of the nic genes responsible for the aerobic degradation of NA in Pseudomonas putida KT2440. The three NA-inducible catabolic operons, i.e. nicAB, encoding the upper pathway that converts NA into 6-hydroxynicotinic acid (6HNA), and the nicCDEFTP and nicXR operons, responsible for channelling 6HNA to the central metabolism, are driven by the Pa, Pc and Px promoters respectively. The nicR regulatory gene encodes a MarR-like protein that represses the activity of the divergent Pc and Px promoters being 6HNA the inducer molecule. A new gene, nicS, that is associated to the nicAB genes in the genomes of different gamma- and beta-Proteobacteria, encodes a TetR-like regulator that represses the activity of Pa in the absence of the NA/6HNA inducers. The NA regulatory circuit in P. putida has evolved an additional repression loop based on the NicR-dependent cross regulation of the nicS gene, thus assuring a tight transcriptional control of the catabolic genes that may prevent depletion of this vitamin B3 when needed for the synthesis of essential cofactors.