title: Mechanism of Vibrio cholerae autoinducer-1 biosynthesis.
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.
authors.affiliation: Department of Molecular Biology and ‡Department of Chemistry, Princeton University, New Jersey 08544, United States.
authors.forename: Yunzhou
authors.initials: Y
authors.lastname: Wei
authors.forename: Lark J
authors.initials: LJ
authors.lastname: Perez
authors.forename: Wai-Leung
authors.initials: WL
authors.lastname: Ng
authors.forename: Martin F
authors.initials: MF
authors.lastname: Semmelhack
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Bassler
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002771:Cholera / Q000382:microbiology; D003001:Cloning, Molecular; D004926:Escherichia coli; D015964:Gene Expression Regulation, Bacterial; D007659:Ketones / Q000378:metabolism*; D007700:Kinetics; D011732:Pyridoxal Phosphate / Q000378:metabolism; D053038:Quorum Sensing / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism*; D013379:Substrate Specificity; D000637:Transaminases / Q000235:genetics / Q000378:metabolism*; D014734:Vibrio cholerae / Q000235:genetics / Q000378:metabolism*
chemical_list: C525620:3-hydroxytridecan-4-one; D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; D007659:Ketones; D011994:Recombinant Proteins; C045561:decanoyl-coenzyme A; D011732:Pyridoxal Phosphate; D012436:S-Adenosylmethionine; D000637:Transaminases