Refactoring Nitrogen Metabolism: The Complex Biogenesis of Metal Cofactors

Prof. Dr. Oliver Einsle (Institute of Biochemistry, University of Freiburg)

The enzymatic machineries for the metabolic conversions of the essential element nitrogen are large, multimeric proteins whose physiological function crucially depends on complex metal-containing cofactors. Besides the structural genes for the actual enzymes, the required operons and gene clusters therefore contain multiple reading frames that encode accessory proteins required for metal center biogenesis, for metal trafficking or as specific chaperones. We are studying the redox enzyme nitrous oxide reductase that catalyzes the reductive cleavage of the critical greenhouse gas N₂O to yield inert N₂ as the final step of bacterial denitrification. N₂O is a major agent of anthropogenic climate change, and nitrous oxide reductase is the only enzyme known to cleave the stable compound. We set out to re-engineer the biosynthetic pathway of the enzyme’s unique active site metal cluster, the [4Cu:2S] Cu_Z site.

Pomowski A, Zumft WG, Kroneck PMH, Einsle O* (2011) N₂O binding at a [4Cu:2S] copper-sulphur cluster in nitrous oxide reductase. Nature 477, 234-237 (BIOSS-Paper).