Related Experiment Video
Updated: Feb 12, 2026

Free Radicals in Chemical Biology: from Chemical Behavior to Biomarker Development
Published on: April 15, 2013
Organometallic and radical intermediates reveal mechanism of diphthamide biosynthesis
Min Dong1, Venkatesan Kathiresan2, Michael K Fenwick1
1Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
Abstract:
Diphthamide biosynthesis involves a carbon-carbon bond-forming reaction catalyzed by a radical S-adenosylmethionine (SAM) enzyme that cleaves a carbon-sulfur (C-S) bond in SAM to generate a 3-amino-3-carboxypropyl (ACP) radical. Using rapid freezing, we have captured an organometallic intermediate with an iron-carbon (Fe-C) bond between ACP and the enzyme's [4Fe-4S] cluster. In the presence of the substrate protein, elongation factor 2, this intermediate converts to an organic radical, formed by addition of the ACP radical to a histidine side chain. Crystal structures of archaeal diphthamide biosynthetic radical SAM enzymes reveal that the carbon of the SAM C-S bond being cleaved is positioned near the unique cluster Fe, able to react with the cluster. Our results explain how selective C-S bond cleavage is achieved in this radical SAM enzyme.
More Related Videos
06:53Author Spotlight: Magnetometric Characterization of Intermediates in the Solid-State Electrochemistry of Redox-Active Metal-Organic Frameworks
Published on: June 9, 2023
09:37Imine Metathesis by Silica-Supported Catalysts Using the Methodology of Surface Organometallic Chemistry
Published on: October 18, 2019
Related Concept Videos
Radical Chain-Growth Polymerization: Mechanism
Properties of Organometallic Compounds
Radical Anti-Markovnikov Addition to Alkenes: Mechanism
The mechanism starts with chain initiation, which involves two steps. In the first chain initiation step, a weak peroxide bond is homolytically cleaved upon mild heating to form two alkoxy radicals. In the second initiation step, a hydrogen atom is abstracted by the alkoxy...
Biosynthesis in Bacteria
Biosynthesis of Polysaccharides
Biosynthesis of Lipids