Presenter: Ethan Murdock
Authors: Ethan Murdock, Aaron Puri
Faculty Advisor: Aaron Puri
Institution: University of Utah
Quorum sensing is the process by which bacterial communities monitor their population densities using signaling molecules in order to coordinate group behavior such as biofilm formation and the production of extracellular natural products. Many Gram-negative bacteria use signaling molecules called acyl-homoserine lactones (acyl-HSLs), which are produced by acyl-HSL synthases. These synthases were generally thought to use acyl carrier protein (ACP)-linked substrates to produce relatively simple signals varying in the length of the acyl chain and substituent at the third carbon. However, more recently a second class of synthases has been characterized that use substrates linked to coenzyme A (CoA). The acyl-HSLs produced by this second class exhibit much greater structural diversity, ranging from branched chain-HSLs to aromatic-HSLs. However, signal production by these synthases often requires extracellular factors to be transformed into acyl-CoAs by acyl-CoA ligase enzymes, which has impeded prediction and characterization of the structures of these signals in the laboratory. To address this, we have created a method to predict the structure of acyl-HSLs produced by CoA-utilizing synthases by measuring the co-occurrence of isofunctional groups of these synthases and CoA ligases across bacterial genomes. Using this co-occurrence method, one can determine which substrate-CoA ligases co-occur with a CoA-utilizing synthase of interest, and predict the structure of the HSL ultimately produced. This will lead to far more efficient characterization of quorum sensing systems, and ultimately expand the known structural diversity of acyl-HSL signals that bacteria use to communicate.