2010 Annual Science Report
Montana State University Reporting | SEP 2009 – AUG 2010
Structure, Reactivity, and Biosynthesis of Cataylic Iron-Sulfur Clusters
We are examining the biosynthesis of complex iron-sulfur cluster to determine the specific chemistry associated with modifying iron-sulfur motifs in biology for different functions. We then relate the chemistry associated with these modifying reactions to reactions that could potentially modify iron-sulfur mineral motifs in the early non-living Earth to promote analogous reactivity.
During the current funding period we have made tremendous progress in the area of [FeFe]-hydrogenase H cluster biosynthesis and nitrogenase biosynthesis. These results have really changed the way in which we think about iron-sulfur enzyme evolution and have laid the groundwork for the development of a completely new experimental line described in the report (see Molecular Paleontology of iron-sulfur enzymes) probing evolution directly with parallel phylogenetic studies on structural and biosynthetic gene products in tandem. Another new line developed from the results this funding period is a thrust area devoted to the evolution and diversity of racial SAM enzyme reactivity also now described as an independent project in the report. Some of the key work reported already this year in the literature or related to the mechanism of H cluster assembly on a scaffold, the role radical SAM enzyme in the synthesis of unique nonprotein ligands and the mechanism of cluster assembly and stepwise maturation on the [FeFe]-hydrogenase structural proteins. We have also examined in collaborative work an reactive intermediate in nitrogen iron-molybdenum cofactor biosynthesis produced by the modification of an iron-sulfur cluster by a radical SAM enzyme and the introduction of a unique non protein ligand. Together these results reveal strong unifying themes in the biosynthesis and maturation of the complex iron-sulfur cluster active sites of Mo-nitrogenases and [FeFe]-hydrogenases. In work published in the Proceedings of the National Academy of Sciences we reported that as in the case of the nitrogenase iron-molydenum cofactor, the [FeFe]-hydrogenase H cluster requires a protein scaffold for complex cluster assembly. In work published in the Journal of the American Chemical Society and in Angewandte Chemie we have been able to show that the unique carbon monoxide and cyanide ligands to Fe in [FeFe]-hydrogenase result from the radical based cleavage of the amino acid tyrosine. This served to prove our previous controversial proposal that carbon monoxide and cyanide ligands could be produced in a concerted manner from amino acid radical decomposition. The results are important and represent biology own version of “ligand assisted catalysis” which has been described to occur when small organics potentially produced by mineral reactivity feed back and directly modify mineral to support new reactivity. Additionally in work published in Nature, through the structural characterization of a key intermediate in cluster biosynthesis we have been able to define the stepwise pathway of cluster biosynthesis.
PROJECT MEMBERS:Joan Broderick
RELATED OBJECTIVES:Objective 3.1
Sources of prebiotic materials and catalysts
Origins and evolution of functional biomolecules
Origins of energy transduction
Origins of cellularity and protobiological systems
Earth's early biosphere.
Biosignatures to be sought in Solar System materials
Biosignatures to be sought in nearby planetary systems