The Department of Chemistry and Physics continues its Seminar series. Details for this week’s talk:
Friday, 11/11/2022
3-4pm Eastern
Grote Hall Room 411
Dr. Constance B. Bailey
Department of Chemistry, University of Tennessee-Knoxville
Strategies to Expand Synthetic Biology with Bacterial Megasynthases
The enzymes responsible for some of the most structurally complex natural products such as polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) have colinear biosynthetic pathways: there is a one-to-one correspondence between metabolite structure and sequence at the DNA and amino acid level. This profoundly enables the ability to program chemistry through alteration of the protein sequence. Our research program seeks to determine the mechanistic principles behind unmet challenges to realize the enormous potential of these biosynthetic pathways through two main thrusts. The first is probing mechanistic questions of the enzymology of megasynthases, especially when we observe unusual biosynthetic transformations. The second is to investigate heterologous expression and screening platforms for refactoring and bioengineering. As part of our efforts to understand and expand heterologous expression, we have been working to develop cell free protein synthesis (CFPS) platforms specific to PKSs and NRPSs by using high throughput reporters such as small fluorescent binding tags and bacterial pigments. Taken together, we see a synergy of enzyme engineering and synthetic biology of host and refactoring choice as essential foundational studies that will the enable reprogramming of large biosynthetic megasynthases. These megasynthases can then be used to generate a diverse range of chemicals including pharmaceuticals, agrochemicals, and other high value bioproducts to accelerate the nascent biomanufacturing sector.
Keenan E. Dungey, PhD
Department Head, Chemistry & Physics