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Acyl homoserine lactone acylases are quorum quenching enzymes that degrade the Gram negative bacterial autoinducerN-acyl homoserine lactone (AHL) and belong to the Ntn-hydrolases superfamily of enzymes. Recent findings reported AHL acylase activity of pencillin V acylases (PVA) which, alongside bile salt hydrolases, are members of the cholyolglycine hydrolase (CGH) family of the Ntn-hydrolases superfamily. The present study reports the unique activity profile of two CGHs from a marine bacteriumShewanella loihica-PV4, designated here asSlCGH1 andSlCGH2, including the structural analysis ofSlCGH1. Both the enzymes exhibit AHL acylase activity while unexpectedly being inactive on standard CGH substrates PenV and bile salts.SlCGH1 differs from known homotetrameric CGHs in being a homodimer displaying a reduced active site volume attributed to loop orientation, which subsequently directs the substrate specificity. Moreover a ligand bound complex structure revealed an unusual bent conformation of the saturated acyl chain bound to the active site and also predicts a single oxyanion hole forming residue during catalysis instead of the usual two residues. Phylogenetic analysis revealsSlCGH1 homologs cluster separate from reported CGHs and AHL acylases. On the whole,SlCGH1 could represent a functionally distinct new sub-class of CGH as an adaptation to the marine environment and its structure could provide the structural framework for understanding such a novel subclass. We also make a modest proposal of a probable evolutionary link between AHL acylases and β lactam acylases based on the overlap in activity and structural features.SignificanceCross-reactivity between AHL acylases and b lactam acylases has been recently identified giving us a vivid glimpse of a possible evolutionary relationship between the phenomena of quorum sensing and antibiotic resistance. We report here the first AHL acylase of the CGH structural framework.SlCGH1 fromShewanella loihicaPV-4 is also the first report of a marine CGH with a unique activity and a new structural subclass of CGH family with AHL acylase activity. This finding highlights the vast diversity of AHL acylases and by extension quorum quenching enzymes as adaptation to different habitats. The results from this study also bolster the link between signal molecules and antibiotics, extending our understanding of the inadequately understood physiological roles of b-lactam acylases. |
