Metalloenzymes encompass the evolutionary oldest and most important classes of enzymes. Roughly half of all enzymes contain metals. The most ancient and most important metalloenzymes contain complex iron-sulphur ([FeS]) clusters. These [FeS] clusters catalyze essential redox reactions thought to have enabled early life on earth. Even today, these metal clusters control key transformations in the global cycle of elements. Hydrogenases catalyze the reversible formation of hydrogen (H2), carbon monoxide dehydrogenases catalyze the interconversion of CO and CO2, while nitrogenases reduce N2 to ammonia (NH3), catalyzing a key step of the global nitrogen cycle.
The structural and chemical basis for the reactivity of these “great clusters”, that catalyze some of the most challenging reactions known in nature have been laid out. However, the recent discoveries that nitrogenase [FeS] clusters directly reduce CO and CO2 to short chain hydrocarbons has challenged our picture of this enzyme (Rebelein et al., Nat Chem Biol, 2017; Rebelein et al., Nat Commun, 2016; Rebelein et al., ChemBioChem, 2015; Rebelein et al., Angew Chem Int Ed Engl, 2014).
These exciting discoveries provoke many questions regarding the diverse (bio)chemistry of nitrogenases, their mechanisms and evolution, particularly about the simplest but under-investigated nitrogenase: the Fe-only nitrogenase.
Our main projects are:
i) Structural and spectroscopic characterization of the Fe-only nitrogenase.
ii) Scrutinizing and engineering nitrogenase activities.
iii) Using natural principals for the construction of artificial metalloenzymes.
We aim to fully understand the innerworkings of complex metalloenzymes to subsequently use these insights to engineer “artificial” metalloenzymes with novel attributes and activities. The long-term goal is to develop synthetic metabolic pathways using these unique reactivities for the production of bulk chemicals, including fertilizer (NH3), hydrocarbons (C2H4, C3H8, C4H10) and hydrogen (H2).