Download MendeleyThe Vibrio cholerae quorum-sensing autoinducer CAI-1: analysis of the biosynthetic enzyme CqsA.
Kelly, R.C., Bolitho, M.E., Higgins, D.A., Lu, W., Ng, W.L., Jeffrey, P.D., Rabinowitz, J.D., Semmelhack, M.F., Hughson, F.M., Bassler, B.L.(2009) Nat Chem Biol 5: 891-895
- PubMed: 19838203
- DOI: https://doi.org/10.1038/nchembio.237
- Primary Citation of Related Structures:
3HQT, 3KKI - PubMed 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.
Organizational Affiliation:
Department of Molecular Biology, Princeton University, New Jersey, USA.
