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Title: Molecular basis for the substrate specificity of quorum signal synthases

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America

In several Proteobacteria, LuxI-type enzymes catalyze the biosynthesis of acyl–homoserine lactones (AHL) signals using S-adenosyl–L-methionine and either cellular acyl carrier protein (ACP)-coupled fatty acids or CoA–aryl/acyl moieties as progenitors. Little is known about the molecular mechanism of signal biosynthesis, the basis for substrate specificity, or the rationale for donor specificity for any LuxI member. As such, here, we present several cocrystal structures of BjaI, a CoA-dependent LuxI homolog that represent views of enzyme complexes that exist along the reaction coordinate of signal synthesis. Complementary biophysical, structure–function, and kinetic analysis define the features that facilitate the unusual acyl conjugation with S-adenosylmethionine (SAM). We also identify the determinant that establishes specificity for the acyl donor and identify residues that are critical for acyl/aryl specificity. These results highlight how a prevalent scaffold has evolved to catalyze quorum signal synthesis and provide a framework for the design of small-molecule antagonists of quorum signaling.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
National Institutes of Health (NIH)
Grant/Contract Number:
GM59026; GM117323
OSTI ID:
1439614
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, Issue 34; ISSN 0027-8424
Publisher:
National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 40 works
Citation information provided by
Web of Science

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Cited By (8)

N-Acylhomoserine lactone-mediated quorum sensing regulates biofilm structure in Methylobacterium populi P-1M, an isolate from a pink-pigmented household biofilm text January 2018
N -Acylhomoserine lactone-mediated quorum sensing regulates biofilm structure in Methylobacterium populi P-1M, an isolate from a pink-pigmented household biofilm journal September 2018
An aryl-homoserine lactone quorum-sensing signal produced by a dimorphic prosthecate bacterium journal July 2018
Revisiting the methionine salvage pathway and its paralogues journal October 2018
Effect of the luxI/R gene on AHL-signaling molecules and QS regulatory mechanism in Hafnia alvei H4 journal December 2019
Insights into β-ketoacyl-chain recognition for β-ketoacyl-ACP utilizing AHL synthases journal January 2018
Cyclodipeptide synthases: a promising biotechnological tool for the synthesis of diverse 2,5-diketopiperazines journal January 2020
Distribution and Genetic Diversity of Genes Involved in Quorum Sensing and Prodigiosin Biosynthesis in the Complete Genome Sequences of Serratia marcescens journal March 2019