Title | The Vibrio cholerae quorum-sensing autoinducer CAI-1: analysis of the biosynthetic enzyme CqsA. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Kelly, RC, Bolitho, ME, Higgins, DA, Lu, W, Ng, W-L, Jeffrey, PD, Rabinowitz, JD, Semmelhack, MF, Hughson, FM, Bassler, BL |
Journal | Nat Chem Biol |
Volume | 5 |
Issue | 12 |
Pagination | 891-5 |
Date Published | 2009 Dec |
Keywords | Amines, 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 Journal | Nat. Chem. Biol. |