Prof. Ben Shen, University of Wisconsin-Madison

How much do we know about polyketide biosynthesis - a journey of constant surprise

Biochemistry Divisional Seminar Series

Polyketides are a large family of structurally diverse natural products found in bacteria, fungi, and plants, and many of them are clinically important drugs. Much of the current research on polyketide biosynthesis is driven by (i) the extraordinary structure, mechanism, and catalytic reactivity of polyketide synthases (PKSs) that provide an unprecedented opportunity to investigate the molecular mechanism of enzyme catalysis, molecular recognition, and protein-protein interaction and (ii) the remarkable flexibility and plasticity of PKSs that allow the production of novel compounds, difficult to access by traditional chemical synthesis, via combinatorial biosynthesis with engineered PKSs. Since the first reports of type II PKS (Nature, 1984, 309, 462), type I PKS (Nature, 1990, 348, 176), and type III PKS (Nature, 1999, 400, 897) from bacteria, the three types of PKSs have provided the molecular basis for the vast structural diversities of the polyketides and the biotechnology platform for engineered biosynthesis of “unnatural” natural products. As the field stumbles into the third decade, how much do we really know about PKSs and polyketide biosynthesis? Selected examples from our current studies will be discussed to argue that PKSs have much greater diversity in both mechanism and structure than currently appreciated, serving as an inspiration in searching for novel PKSs and polyketide biosynthetic machineries.

For more information contact Prof. Wendy Kelly (404-385-1154).