Mechanism of Vibrio cholerae autoinducer-1 biosynthesis

Yunzhou Wei, Lark J. Perez, Wai Leung Ng, Martin F. Semmelhack, Bonnie L. Bassler

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74 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)356-365
Number of pages10
JournalACS Chemical Biology
Volume6
Issue number4
DOIs
StatePublished - Apr 15 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine

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    Wei, Y., Perez, L. J., Ng, W. L., Semmelhack, M. F., & Bassler, B. L. (2011). Mechanism of Vibrio cholerae autoinducer-1 biosynthesis. ACS Chemical Biology, 6(4), 356-365. https://doi.org/10.1021/cb1003652