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Biochemistry Department Seminar – Dr. Gavin Williams
“Synthetic Biology Approach to New-to-Nature Natural Products”
Dr. Gavin Williams
NCSU Department of Chemistry
Abstract: Many clinically used drugs are derived from secondary metabolites that are biosynthesized in a modular fashion by the selection and condensation of small-molecule building blocks. Chimeric biosynthetic pathways can be constructed to produce analogs for drug discovery. Yet, the scope and utility of this combinatorial approach are limited by the inherent substrate specificity and poor functional modularity of most biosynthetic machinery. Here, we describe a comprehensive program of enzyme engineering, biosensor-guided directed evolution, and synthetic biology to construct artificial bacterial strains capable of producing complex natural products modified with unnatural chemical functionality. Our synthetic biology approach extends the synthetic capabilities of natural product diversification strategies and provides a deeper understanding of the molecular basis of specificity in complex molecular assemblies.