Genome Mining

Bacteria communicate with one another using small organic molecules as chemical messages. These molecules regulate the ability of bacterial pathogens to infect their hosts, virulence. Researchers in the Li Group study the small molecule messages produced by Pseudomonas, an important family of pathogens that infect plants, animals, and humans. The Pseudomonas virulence factor, pvf, operon is widely conserved in Pseudomonas and encodes four biosynthetic enzymes that synthesize small molecules. The chemical structures of these molecules were unknown.

The Li group members set out to identify small molecules produced by pvf-encoded enzymes using the insect pathogen P. entomophila as a model. In a study published in Organic Letters, they identify a family of pyrazine N-oxides and a novel dihydropyrazine N-oxide metabolite synthesized by two of the four pvf-encoded enzymes. These enzymes are related to those essential for making the antibiotics vancomycin and chloramphenicol.

This works shows that the pvf-encoded enzymes catalyze unique chemistry in the construction of (dihydro)pyrazine-N-oxides. It also sets the stage for exploring the signaling activity of the metabolites produced by the pvf virulence pathway.