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
KeywordsAmines, Binding Sites, Coenzyme A-Transferases, Ketones, Models, Molecular, Mutagenesis, Site-Directed, Pyridoxal Phosphate, Quorum Sensing, Signal Transduction, Substrate Specificity, Vibrio cholerae
Abstract

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.

Alternate JournalNat. Chem. Biol.