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

Abstract

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 γ- and β-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.

The Bordetella bronchiseptica nic locus encodes a nicotinic acid degradation pathway and the 6‐hydroxynicotinate‐responsive regulator BpsR

“…The P. putida nicAB genes are repressed by NicS, which responds to the Na or 6‐HNa inducers, resulting in derepression. P. putida NicR exerts negative control at the nicC‐nicX divergent control region and is responsive only to 6‐HNa (Jiménez et al ., ).…”

“…P. putida NicR and Bordetella BpsR are members of the MarR family of regulators that typically bind effectors that modify their activity. Based on the present studies and those of P. putida (Jiménez et al ., ), BpsR, like NicR, represses transcription by binding to upstream control regions of target nic genes. When BpsR binds the 6‐HNa inducer, it loses its DNA‐binding activity and the nic genes are expressed (derepressed).…”

The translational repressor Crc controls the Pseudomonas putida benzoate and alkane catabolic pathways using a multi‐tier regulation strategy

“…. For example, in the pathways involved in the assimilation of the aromatic non‐preferred compounds vanillate (Jiménez et al ., ; ) and nicotinate (Jiménez et al ., ; ), Crc targets likely exist in the mRNA of the genes coding for the transcriptional activators of the pathways, of genes involved in the uptake of these aromatic compounds, and of genes corresponding to the first enzymes in their catabolic pathways (Fig. ).…”

The TetR Family of Regulators

“…MdoR regulates expression of the mdo gene, which is required for oxidation of methanol. The TFRs NicS, PaaR, and RolR are involved in the regulation of metabolism pathways for nicotinic acid, phenyl acetic acid, and resorcinol, respectively (148)(149)(150). In each case, the TFR has been shown to interact with the molecule being degraded or a catabolic intermediate.…”