LsrF, A Coenzyme A-Dependent Thiolase, Catalyzes The Terminal Step In Processing The Quorum Sensing Signal Autoinducer-2
Proceedings Of The National Academy Of Sciences
The quorum sensing signal autoinducer-2 (AI-2) regulates important bacterial behaviors, including biofilm formation and the production of virulence factors. Some bacteria, such as Escherichia coli, can quench the AI-2 signal produced by a variety of species present in the environment, and thus can influence AI-2–dependent bacterial behaviors. This process involves uptake of AI-2 via the Lsr transporter, followed by phosphorylation and consequent intracellular sequestration. Here we determine the metabolic fate of intracellular AI-2 by characterizing LsrF, the terminal protein in the Lsr AI-2 processing pathway. We identify the substrates of LsrF as 3-hydroxy-2,4-pentadione-5-phosphate (P-HPD, an isomer of AI-2-phosphate) and coenzyme A, determine the crystal structure of an LsrF catalytic mutant bound to P-HPD, and identify the reaction products. We show that LsrF catalyzes the transfer of an acetyl group from P-HPD to coenzyme A yielding dihydroxyacetone phosphate and acetyl-CoA, two key central metabolites. We further propose that LsrF, despite strong structural homology to aldolases, acts as a thiolase, an activity previously undescribed for this family of enzymes. With this work, we have fully characterized the biological pathway for AI-2 processing in E. coli, a pathway that can be used to quench AI-2 and control quorum-sensing–regulated bacterial behaviors.
cell–cell signaling, quorum quenching, bacterial communication, metabolic flux
J. C. Marques; Il Kyu Oh , '14; Daniel C. Ly , '12; P. Lamosa; M. R. Ventura; Stephen T. Miller; and K. B. Xavier.
"LsrF, A Coenzyme A-Dependent Thiolase, Catalyzes The Terminal Step In Processing The Quorum Sensing Signal Autoinducer-2".
Proceedings Of The National Academy Of Sciences.