L-Lysine Decarboxylase and Cadaverine Gamma-Glutamylation Pathways in Pseudomonas Aeruginosa PAO1

In comparison to other Pseudomonas, P. aeruginosa grows poorly in L-lysine as a sole source of nutrient while fast growth mutants can be obtained. The proposed catabolic pathway involves lysine decarboxylation to cadaverine and its subsequent degradation through -glutamylation pathway to -aminovalerate and glutarate. The lysine decarboxylase A (ldcA) gene, previously identified as a member of the ArgR regulon of L-arginine metabolism, was found essential for Llysine catabolism. The ldcA gene encodes a decarboxylase which takes L-lysine but not Larginine as substrate. Contrarily, the ldcA expression was inducible by L-arginine but not by Llysine. This peculiar arginine control on lysine utilization was also noted from uptake experiments. The lack of lysine-responsive control on lysine catabolism and its tight connection to arginine regulatory network provided an explanation of lysine as poor nutrient for P. aeruginosa. Catabolism of cadaverine, a product from lysine decarboxylation, was investigated and compared to that of putrescine, another diamine of similar biochemical properties that is derived from arginine and ornithine. While the -glutamylation pathway was first reported in E. coli for putrescine utilization, an expanded version of this pathway was found in P. aeruginosa with redundant enzymes for polyamine degradation. The PauR protein was identified as a transcriptional repressor of genes for the catabolism of putrescine and cadaverine, as well as their corresponding downstream metabolites, -aminobutyrate (GABA) and -aminovalerate (AMV). PauR shows distinct dimer configuration after glutaraldehyde crosslinkage, and possible conformational changes could be triggered by the presence of putrescine and cadaverine, but not GABA. A newly identified ABC transport system, encoded by the agtABCD operon, was found important for the uptake of GABA and AMV; and expression of which is controlled by the AgtSR two-component system. The CbrAB two-component system was proposed to regulate the catabolite repression control protein Crc through a small RNA CrcZ. A consensus CbrB recognition sequence was proposed based on the conserved palindromic nucleotide sequence in the upstream activating sequence of the crcZ promoter. Genetic studies indicated utilization of arginine, lysine and diamines (but not histidine, GABA and AMV) might be under CbrAB regulation through the CbrAB/CrcZ/Crc system in P. aeruginosa. INDEX WORDS: Pseudomonas, Lysine, Arginine, Cadaverine, Putrescine, GABA, AMV, Catabolism, Decarboxylation, -Glutamylation, Uptake, Regulation, Catabolite Repression, TwoComponent System. L-LYSINE DECARBOXYLASE AND CADAVERINE -GLUTAMYLATION PATHWAYS IN PSEUDOMONAS AERUGINOSA PAO1