W. N. Lacey Lectureship in Chemical Engineering

Many polyketide antibiotics are synthesized by multi-enzyme systems that operate in an assembly line-like fashion. Their apparently modular architecture has opened the door to engineering of new antibiotics by rationally manipulating the DNA encoding these megasynthases. Elucidating the structures and mechanisms of these assembly lines represents a challenging frontier in physical and chemical enzymology. While much progress has been made on some fronts over the past three decades, our understanding of other fundamental features of these enzymatic assembly lines is rudimentary. My lecture will provide an overview of what we know and what we don't know, with a focus on the 6-deoxyerythronolide B synthase, a prototypical assembly-line polyketide synthase.