The Vibrio cholerae quorum-sensing autoinducer CAI-1: analysis of the biosynthetic enzyme CqsA
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 {ge}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.
- Authors:
- Publication Date:
- Research Org.:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Org.:
- DOE - OFFICE OF SCIENCE
- OSTI Identifier:
- 1020115
- Report Number(s):
- BNL-95964-2011-JA
Journal ID: ISSN 1552-4450; TRN: US201116%%96
- DOE Contract Number:
- DE-AC02-98CH10886
- Resource Type:
- Journal Article
- Journal Name:
- Nature Chemical Biology
- Additional Journal Information:
- Journal Volume: 5; Journal Issue: 12; Journal ID: ISSN 1552-4450
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; BIOSYNTHESIS; CHOLERA; COENZYMES; DISEASES; ENZYMES; PRODUCTION; PYRIDOXAL; REACTION KINETICS; SUBSTRATES; TRANSFERASES; VIRULENCE; national synchrotron light source
Citation Formats
Kelly, R, Bolitho, M, Higgins, D, Lu, W, Ng, W, Jeffrey, P, Rabinowitz, J, Semmelhack, M, Hughson, F, and Bassler, B. The Vibrio cholerae quorum-sensing autoinducer CAI-1: analysis of the biosynthetic enzyme CqsA. United States: N. p., 2009.
Web. doi:10.1038/nchembio.237.
Kelly, R, Bolitho, M, Higgins, D, Lu, W, Ng, W, Jeffrey, P, Rabinowitz, J, Semmelhack, M, Hughson, F, & Bassler, B. The Vibrio cholerae quorum-sensing autoinducer CAI-1: analysis of the biosynthetic enzyme CqsA. United States. https://doi.org/10.1038/nchembio.237
Kelly, R, Bolitho, M, Higgins, D, Lu, W, Ng, W, Jeffrey, P, Rabinowitz, J, Semmelhack, M, Hughson, F, and Bassler, B. 2009.
"The Vibrio cholerae quorum-sensing autoinducer CAI-1: analysis of the biosynthetic enzyme CqsA". United States. https://doi.org/10.1038/nchembio.237.
@article{osti_1020115,
title = {The Vibrio cholerae quorum-sensing autoinducer CAI-1: analysis of the biosynthetic enzyme CqsA},
author = {Kelly, R and Bolitho, M and Higgins, D and Lu, W and Ng, W and Jeffrey, P and Rabinowitz, J and Semmelhack, M and Hughson, F and Bassler, B},
abstractNote = {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 {ge}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.},
doi = {10.1038/nchembio.237},
url = {https://www.osti.gov/biblio/1020115},
journal = {Nature Chemical Biology},
issn = {1552-4450},
number = 12,
volume = 5,
place = {United States},
year = {Thu Jan 01 00:00:00 EST 2009},
month = {Thu Jan 01 00:00:00 EST 2009}
}