Mechanism of Vibrio cholerae autoinducer-1 biosynthesis.

TitleMechanism of Vibrio cholerae autoinducer-1 biosynthesis.
Publication TypeJournal Article
Year of Publication2011
AuthorsWei, Y, Perez, LJ, Ng, W-L, Semmelhack, MF, Bassler, BL
JournalACS Chem Biol
Volume6
Issue4
Pagination356-65
Date Published2011 Apr 15
ISSN1554-8937
KeywordsAcyl Coenzyme A, Bacterial Proteins, Cholera, Cloning, Molecular, Escherichia coli, Gene Expression Regulation, Bacterial, Ketones, Kinetics, Pyridoxal Phosphate, Quorum Sensing, Recombinant Proteins, S-Adenosylmethionine, Substrate Specificity, Transaminases, Vibrio cholerae
Abstract

<p>Vibrio cholerae, the causative agent of the disease cholera, uses a cell to cell communication process called quorum sensing to control biofilm formation and virulence factor production. The major V. cholerae quorum-sensing signal CAI-1 has been identified as (S)-3-hydroxytridecan-4-one, and the CqsA protein is required for CAI-1 production. However, the biosynthetic route to CAI-1 remains unclear. Here we report that (S)-adenosylmethionine (SAM) is one of the two biosynthetic substrates for CqsA. CqsA couples SAM and decanoyl-coenzyme A to produce a previously unknown but potent quorum-sensing molecule, 3-aminotridec-2-en-4-one (Ea-CAI-1). The CqsA mechanism is unique; it combines two enzymatic transformations, a β,γ-elimination of SAM and an acyltransferase reaction into a single PLP-dependent catalytic process. Ea-CAI-1 is subsequently converted to CAI-1, presumably through the intermediate tridecane-3,4-dione (DK-CAI-1). We propose that the Ea-CAI-1 to DK-CAI-1 conversion occurs spontaneously, and we identify the enzyme responsible for the subsequent step: conversion of DK-CAI-1 into CAI-1. SAM is the substrate for the synthesis of at least three different classes of quorum-sensing signal molecules, indicating that bacteria have evolved a strategy to leverage an abundant substrate for multiple signaling purposes.</p>

DOI10.1021/cb1003652
Alternate JournalACS Chem. Biol.
PubMed ID21197957
PubMed Central IDPMC3077805
Grant List5R01AI054442 / AI / NIAID NIH HHS / United States
5R01GM065859 / GM / NIGMS NIH HHS / United States
GM082061 / GM / NIGMS NIH HHS / United States
R01 AI054442 / AI / NIAID NIH HHS / United States