MOMIMIC · Multi-layered biomimetics of lytic polysaccharide monooxygenases

Multi-layered biomimetics of lytic polysaccharide monooxygenases

Lytic polysaccharide monooxygenases (LPMO) are a family of enzymes that use oxygen or hydrogen peroxide to oxidatively cleave the glycosidic bonds in recalcitrant polysaccharides. This has been shown to greatly enhance the enzymatic degradation of cellulose, making these enzymes of significant interest for the conversion of lignocellulosic biomass into biofuels or commodity chemicals. The cleavage reaction occurs via hydroxylation of the 1- or 4-position C-H bonds flanking the glycosidic linkage. As the dissociation energy for these bonds is quite high (near 100 kcal/mol), a better understanding of all of the factors that allow LPMO to perform this reaction is important not just from the standpoint of biomass conversion, but also for developing synthetic catalysts able to perform similar transformations. The active sites of all members of the LPMO family contain a mononuclear copper site with the metal bound in a T-shaped N3 coordination environment, described as the histidine brace, comprised of the amine and imidazole of an N-terminal histidine and another histidine imidazole. Though the specific features of the histidine brace that contribute to LPMO reactivity are not fully understood, the similar binding site in particulate methane monooxygenase indicates it may be essential for the demonstrated oxidative power of the enzymes. Additionally, beyond the active site, multiple amino acids in the second coordination sphere are also thought to contribute to the reactivity. Studying the role these structural features with synthetic models of the active site could lead to a better understanding of the enzyme and help address multiple questions related to the mechanism of the oxidation. Still, despite the apparent simplicity of the coordination environment, no model complexes to date have been reported that exactly replicate the histidine brace. The objectives of MOMIMIC are to address the challenges of developing structural models through the use of molecular scaffolds based on aromatic oligoamide foldamers to engineer ligands with fully-defined multi-layered coordination environments and to study the properties and reactivity of the complexes with copper. New synthetic approaches for obtaining imidazole/histamine functionalized monomers and for their incorporation into oligomers are explored leading to a series of ligands. Through metalation, the spectroscopic properties of the resulting complexes can be compared to both the enzyme and smaller model systems to see the effects of the scaffold. By studying the reactivity of these systems with oxygen, these complexes can eventually provide important spectroscopic models for better understanding of LPMO.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз