Areas of Interest
Bacteria craft complex ketide- and amino acid-containing biomolecules in an assembly-line fashion using polyketide synthases (PKS) and/or nonribosomal peptide synthetases (NRPS). These products are extremely diverse and have a range of bioactivities, such as the NRPS-made antibiotic vancomycin, or the anticancer epothilones, which are produced by a mix of PKS and NRPS modules. In this assembly line system, each module passes its intermediate to the next via complementary docking domains that are unique to each interface. However, our collaborator Dr. Bill Gerwick recently discovered a novel example of PKS/NRPS multiplexing, where a module in the middle of the pathway can connect with multiple downstream modules to form multiple products. This breaks the paradigm in which pathways flow in a linear order with no branches. I am investigating the factors that control downstream pathway selection by studying docking affinities in vitroand characterizing these interactions with X-ray crystallography. This discovery opens many exciting doors, including the strategy of introducing redundant docking domains into natural pathways to create novel compounds.