Chemistry Seminar Presented by Prof. Ken Yokoyama (Duke University) How enzymes navigate challenging chemistry: Lessons from cofactor and antibiotic biosynthesis

The Department of Chemistry is excited to host Prof. Ken Yokoyama, Duke University, on Tuesday, September 1, 2026, at 11:40 am for a departmental seminar.

To learn more about Prof. Ken Yokoyama, Duke University's research, please visit: https://sites.duke.edu/yokoyamalab/

Title:
How enzymes navigate challenging chemistry: Lessons from cofactor and antibiotic biosynthesis

Abstract:
Many biologically important small molecules contain unusual structures assembled through reactions that pose formidable chemical challenges. My group investigates how enzymes-particularly metalloenzymes and catalysts of complex rearrangements-accomplish these transformations and how their chemistry might be harnessed for drug and biocatalyst development. I will focus on two systems: the biosynthesis of the molybdenum cofactor (Moco) and peptide antibiotics. Moco biosynthesis begins with one of nature's most intricate atomic rearrangements: the transformation of guanosine 5′-triphosphate (GTP) into the first pterin intermediate, pyranopterin cyclic monophosphate (cPMP). My group discovered that MoaA, a radical SAM enzyme, catalyzes the chemically challenging 3′,8-cyclization of GTP, whereas MoaC catalyzes the subsequent complex rearrangement to produce cPMP. Our recent studies further revealed how MoaA controls radical initiation and reaction trajectory and how MoaC proceeds through unexpected covalent enzyme-substrate intermediates. These findings reveal potentially generalizable strategies by which enzymes control complex chemical transformations. I will also discuss two evolutionarily related but functionally distinct radical SAM enzymes that construct the peptide antibiotics darobactin and dynobactin. We found that DarE is the first radical SAM enzyme known to use O2 as a cosubstrate, employing it for ether-bond formation. Because radical SAM enzymes contain O2-sensitive iron-sulfur clusters and are generally associated with anaerobic chemistry, this discovery was unexpected and revealed a previously unrecognized family of radical SAM oxygenases. By contrast, DynA functions independently of O2 and catalyzes unusual radical-mediated C-N and C-C crosslinking reactions. I will discuss how these distinct catalytic activities emerged during evolution and how they might be exploited in future biocatalyst development.

Seminar hosted by: Prof. Emily Derbyshire and Prof. Weitao Yang