Introduction to the Thematic Minireview Series on Radical S-Adenosylmethionine (SAM) Enzymes

Ruma Banerjee

doi:10.1074/jbc.r114.630251

Abstract

In the early days, radical enzyme reactions that use S-adenosylmethionine (SAM) coordinated to an Fe-S cluster, which Perry Frey described as a "poor man's coenzyme B12," were believed to be relatively rare chemical curiosities. Today, bioinformatics analyses have revealed the wide prevalence and sheer numbers of radical SAM enzymes, conferring superfamily status. In this thematic minireview series, the JBC presents six articles on radical SAM enzymes that accomplish wide-ranging chemical transformations. We learn that despite the diversity of the reactions catalyzed, family members share some common structural and mechanistic themes. Still in its infancy, continued explorations promise to be fertile grounds for discoveries that will undoubtedly further broaden our understanding of the catalytic repertoire and deepen our understanding of the chemical strategies used by radical SAM enzymes.

Highlights

In the third article in this series, Begley and co-workers (3) discuss the role of radical SAM enzymes in facilitation of complex radical rearrangements during the synthesis of thiamin, deazaflavin, menaquinone, molybdopterin, and heme cofactors
The authors discuss how the relatively long lifetime of the 5Ј-deoxyadenosyl radical, together with its intrinsic reactivity, opens up a range of novel reactions including fragmentation, double bond addition, and radical propagation, some of which are unprecedented in organic chemistry
In the fourth article in this series, Broderick and co-workers (4) discuss the current state of our knowledge about radical SAM enzymes involved in the synthesis of the FeMo-cofactor of nitrogenase, which contains a central carbon atom, the iron subcluster coordinated by cyanide, CO, and dithiomethylamine in [FeFe]-hydrogenase and the iron center with CO and guanylylpyridinol ligands in [Fe]-hydrogenase

Summary

Introduction

In the third article in this series, Begley and co-workers (3) discuss the role of radical SAM enzymes in facilitation of complex radical rearrangements during the synthesis of thiamin, deazaflavin, menaquinone, molybdopterin, and heme cofactors. The authors discuss how the relatively long lifetime of the 5Ј-deoxyadenosyl radical, together with its intrinsic reactivity, opens up a range of novel reactions including fragmentation, double bond addition, and radical propagation, some of which are unprecedented in organic chemistry. The elaboration of unusual organometallic cofactors requires unusual enzymes.

Results

Conclusion