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2011 Annual Science Report

Montana State University Reporting  |  SEP 2010 – AUG 2011

Radical SAM Chemistry and Biological Ligand Accelerated Catalysis

Project Summary

A number of key reactions in biological systems are catalyzed by iron-sulfur enzymes. Iron-sulfur clusters in biology have a number of features in common with iron-sulfur minerals and their derivatives. We are using iron sulfur motifs as a model system to understand how chemistry in the abiotic mineral world was incorporated into biology on a path to the origin of life. We have found that iron-sulfur motifs in biology are synthesized and modified by reactions and mechanisms that we envision minerals could have been modified on the early prebiotic Earth. The results have had a profound impact on our ability to understand a stepwise trajectory from the nonliving to the living Earth.

4 Institutions
3 Teams
11 Publications
0 Field Sites
Field Sites

Project Progress

Iron-sulfur clusters are thought to be among the most ancient cofactors in living systems. The Fe-S enzyme thrust is focused on examining the structure, mechanism, and biosynthesis of the complex Fe-S enzymes nitrogenase and hydrogenase. Exciting new results have identified important links between the biosynthesis of the H-cluster and FeMo-co and have provided direct links to the evolution of Fe-S biocatalysts from their mineral-based precursors.

Phylogeny of radical SAM enzymes involved in complex metallocofactor assembly (left). HydE and HydG are involved in H-cluster assembly and NifB is responsible for synthesizing NifB-co, a precursor to FeMo-co. The hypothetical model for H-cluster biosynthesis in [FeFe] hydrogenase maturation (top, right). The evolutionary history of HydE and HydG, relative to other members of the radical SAM protein family, suggests that the emergence of HydE predates the emergence of HydG (left). We propose that this finding supports the hypothesis that HydE performs its chemical modifications prior to HydG during the stepwise synthesis of the H-cluster. HydE utilizes SAM and an unidentified substrate to presumably alkylate a [2Fe–2S] precursor on the scaffold HydF, followed by delivery of CO and CN− via interaction with HydG. In a final step, the 2Fe subcluster on HydF is translocated to the immature structural protein, HydAΔEFG, through the migration of the 2Fe subcluster through a cationic channel on HydA after which the movement of two loop regions close the channel. The biochemical model for FeMo-co biosynthesis in nitrogenase maturation (bottom, right). NifB utilizes SAM based radical chemistry to build NifB-co from iron–sulfur cluster precursors. NifB-co is transferred to the scaffold NifEN where molybdenum and homocitrate are introduced to synthesize FeMo-co, which is then transferred to NifDK to yield nitrogenase. Atom colors: maroon (Fe), orange (S), black©, red (O), blue (N), cyan (Mo), pink (unidentified, probably either N or O in the H-cluster and either C, N, or O in FeMo-co).