Title | Mechanism of Vibrio cholerae autoinducer-1 biosynthesis. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Wei, Y, Perez, LJ, Ng, W-L, Semmelhack, MF, Bassler, BL |
Journal | ACS Chem Biol |
Volume | 6 |
Issue | 4 |
Pagination | 356-65 |
Date Published | 2011 Apr 15 |
ISSN | 1554-8937 |
Keywords | Acyl 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> |
DOI | 10.1021/cb1003652 |
Alternate Journal | ACS Chem Biol |
PubMed ID | 21197957 |
PubMed Central ID | PMC3077805 |
Grant List | R01 GM065859 / GM / NIGMS NIH HHS / United States 5R01AI054442 / AI / NIAID NIH HHS / United States GM082061 / GM / NIGMS NIH HHS / United States R01 AI054442 / AI / NIAID NIH HHS / United States F32 GM082061 / GM / NIGMS NIH HHS / United States 5R01GM065859 / GM / NIGMS NIH HHS / United States |