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A Novel Subfamily of Bacterial AAT-Fold Basic Amino Acid Decarboxylases and Functional Characterization of Its First Representative: Pseudomonas aeruginosa LdcA.

ABSTRACT: Polyamines are small amino-acid derived polycations capable of binding negatively charged macromolecules. Bacterial polyamines are structurally and functionally diverse, and are mainly produced biosynthetically by pyridoxal-5-phosphate-dependent amino acid decarboxylases referred to as Lysine-Arginine-Ornithine decarboxylases (LAOdcs). In a phylogenetically limited group of bacteria, LAOdcs are also induced in response to acid stress. Here, we performed an exhaustive phylogenetic analysis of the AAT-fold LAOdcs which showcased the ancient nature of their short forms in Cyanobacteria and Firmicutes, and emergence of distinct subfamilies of long LAOdcs in Proteobacteria. We identified a novel subfamily of lysine decarboxylases, LdcA, ancestral in Betaproteobacteria and Pseudomonadaceae. We analyzed the expression of LdcA from Pseudomonas aeruginosa, and uncovered its role, intimately linked to cadaverine (Cad) production, in promoting growth and reducing persistence of this multidrug resistant human pathogen during carbenicillin treatment. Finally, we documented a certain redundancy in the function of the three main polyamines-Cad, putrescine (Put), and spermidine (Spd)-in P. aeruginosa by demonstrating the link between their intracellular level, as well as the capacity of Put and Spd to complement the growth phenotype of the ldcA mutant.

SUBMITTER: Carriel D

PROVIDER: S-EPMC6257575 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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A Novel Subfamily of Bacterial AAT-Fold Basic Amino Acid Decarboxylases and Functional Characterization of Its First Representative: Pseudomonas aeruginosa LdcA.

Carriel Diego D Simon Garcia Pierre P Castelli Florence F Lamourette Patricia P Fenaille François F Brochier-Armanet Céline C Elsen Sylvie S Gutsche Irina I

Genome biology and evolution 20181101 11

Polyamines are small amino-acid derived polycations capable of binding negatively charged macromolecules. Bacterial polyamines are structurally and functionally diverse, and are mainly produced biosynthetically by pyridoxal-5-phosphate-dependent amino acid decarboxylases referred to as Lysine-Arginine-Ornithine decarboxylases (LAOdcs). In a phylogenetically limited group of bacteria, LAOdcs are also induced in response to acid stress. Here, we performed an exhaustive phylogenetic analysis of the ...[more]

PMID: 30321344

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Project description:The quinolone ring is a common core structure of natural products exhibiting antimicrobial, cytotoxic, and signaling activities. A prominent example is the Pseudomonas quinolone signal (PQS), a quorum-sensing signal molecule involved in the regulation of virulence of Pseudomonas aeruginosa The key reaction to quinolone inactivation and biodegradation is the cleavage of the 3-hydroxy-4(1H)-quinolone ring, catalyzed by dioxygenases (HQDs), which are members of the α/β-hydrolase fold superfamily. The α/β-hydrolase fold core domain consists of a β-sheet surrounded by α-helices, with an active site usually containing a catalytic triad comprising a nucleophilic residue, an acidic residue, and a histidine. The nucleophile is located at the tip of a sharp turn, called the "nucleophilic elbow." In this work, we developed a search workflow for the identification of HQD proteins from databases. Search and validation criteria include an [H-x(2)-W] motif at the nucleophilic elbow, an [HFP-x(4)-P] motif comprising the catalytic histidine, the presence of a helical cap domain, the positioning of the triad's acidic residue at the end of β-strand 6, and a set of conserved hydrophobic residues contributing to the substrate cavity. The 161 candidate proteins identified from the UniProtKB database originate from environmental and plant-associated microorganisms from all domains of life. Verification and characterization of HQD activity of 9 new candidate proteins confirmed the reliability of the search strategy and suggested residues correlating with distinct substrate preferences. Among the new HQDs, PQS dioxygenases from Nocardia farcinica, N. cyriacigeorgica, and Streptomyces bingchenggensis likely are part of a catabolic pathway for alkylquinolone utilization.IMPORTANCE Functional annotation of protein sequences is a major requirement for the investigation of metabolic pathways and the identification of sought-after biocatalysts. To identify heterocyclic ring-cleaving dioxygenases within the huge superfamily of α/β-hydrolase fold proteins, we defined search and validation criteria for the primarily motif-based identification of 3-hydroxy-4(1H)-quinolone 2,4-dioxygenases (HQD). HQDs are key enzymes for the inactivation of metabolites, which can have signaling, antimicrobial, or cytotoxic functions. The HQD candidates detected in this study occur particularly in environmental and plant-associated microorganisms. Because HQDs active toward the Pseudomonas quinolone signal (PQS) likely contribute to interactions within microbial communities and modulate the virulence of Pseudomonas aeruginosa, we analyzed the catalytic properties of a PQS-cleaving subset of HQDs and specified characteristics to identify PQS-cleaving dioxygenases within the HQD family.

Dataset Information

A Novel Subfamily of Bacterial AAT-Fold Basic Amino Acid Decarboxylases and Functional Characterization of Its First Representative: Pseudomonas aeruginosa LdcA.

Publications

A Novel Subfamily of Bacterial AAT-Fold Basic Amino Acid Decarboxylases and Functional Characterization of Its First Representative: Pseudomonas aeruginosa LdcA.

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