The Vibrio cholerae quorum-sensing autoinducer CAI-1: analysis of the biosynthetic enzyme CqsA.

TitleThe Vibrio cholerae quorum-sensing autoinducer CAI-1: analysis of the biosynthetic enzyme CqsA.
Publication TypeJournal Article
Year of Publication2009
AuthorsKelly, RC, Bolitho, ME, Higgins, DA, Lu, W, Ng, W-L, Jeffrey, PD, Rabinowitz, JD, Semmelhack, MF, Hughson, FM, Bassler, BL
JournalNat Chem Biol
Volume5
Issue12
Pagination891-5
Date Published2009 Dec
ISSN1552-4469
KeywordsAmines, Binding Sites, Coenzyme A-Transferases, Ketones, Models, Molecular, Mutagenesis, Site-Directed, Pyridoxal Phosphate, Quorum Sensing, Signal Transduction, Substrate Specificity, Vibrio cholerae
Abstract

<p>Vibrio cholerae, the bacterium that causes the disease cholera, controls virulence factor production and biofilm development in response to two extracellular quorum-sensing molecules, called autoinducers. The strongest autoinducer, called CAI-1 (for cholera autoinducer-1), was previously identified as (S)-3-hydroxytridecan-4-one. Biosynthesis of CAI-1 requires the enzyme CqsA. Here, we determine the CqsA reaction mechanism, identify the CqsA substrates as (S)-2-aminobutyrate and decanoyl coenzyme A, and demonstrate that the product of the reaction is 3-aminotridecan-4-one, dubbed amino-CAI-1. CqsA produces amino-CAI-1 by a pyridoxal phosphate-dependent acyl-CoA transferase reaction. Amino-CAI-1 is converted to CAI-1 in a subsequent step via a CqsA-independent mechanism. Consistent with this, we find cells release > or =100 times more CAI-1 than amino-CAI-1. Nonetheless, V. cholerae responds to amino-CAI-1 as well as CAI-1, whereas other CAI-1 variants do not elicit a quorum-sensing response. Thus, both CAI-1 and amino-CAI-1 have potential as lead molecules in the development of an anticholera treatment.</p>

DOI10.1038/nchembio.237
Alternate JournalNat. Chem. Biol.
PubMed ID19838203
PubMed Central IDPMC2847429
Grant ListAI054442 / AI / NIAID NIH HHS / United States
AI069326 / AI / NIAID NIH HHS / United States
GM065859 / GM / NIGMS NIH HHS / United States
P30 EB009998 / EB / NIBIB NIH HHS / United States
R01 AI054442 / AI / NIAID NIH HHS / United States
R01 AI054442-07 / AI / NIAID NIH HHS / United States
R01 GM065859 / GM / NIGMS NIH HHS / United States
R01 GM065859-07 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States