Nature has provided us with an arsenal of agents that have proven clinically useful in the treatment of many human diseases, and this is particularly apparent for infectious diseases and cancer. Resistance to current anticancer and antimicrobial chemotherapies will always necessitate the discovery and development of additional therapeutic compounds, both by screening of natural products and by synthetic design. Biosynthetic engineering is a promising tool that could be coupled with these proven techniques to generate novel bioactive metabolites. Dr. Kelly's group examines natural products biosynthesis and its applications from chemical and microbiological perspectives.
Dr. Kelly's group is interested in the biosynthesis of polyketide and nonribosomal peptide antibiotics in addition to the biosynthesis of post-translationally modified peptide antibiotics. We aim to understand the assembly of central scaffolds that appear in families of metabolites that vary in their biological activity according to unique peripheral modifications. This requires a detailed understanding of the enzymes responsible for construction of these molecules, including their catalytic mechanism and substrate specificity. Strategies and techniques from organic chemistry, biochemistry, molecular biology, and microbiology will be infused together to accomplish this task. Ultimately, we will apply the information gleaned from these studies to direct the biosynthesis of designer metabolites possessing antimicrobial or anticancer activities.