Award details

Expanding the substrate and biological scopes of lytic polysaccharide monooxygenases

Reference	BB/V004069/1
Principal Investigator / Supervisor	Professor Paul Walton
Co-Investigators / Co-Supervisors	Professor Gideon Davies, Dr Sean Sweeney
Institution	University of York
Department	Chemistry
Funding type	Research
Value (£)	554,937
Status	Current
Type	Research Grant
Start date	01/09/2021
End date	30/11/2024
Duration	39 months

Abstract

Recent work has highlighted the power of a new group of copper-dependent monooxygenases termed lytic polysaccharide monooxygenases, LPMOs. These enzymes harness the power of a "histidine brace" active centre, to perform oxygenations on the most unreactive C-H bonds present in Nature. LPMOs have been a truly disruptive technology in the biotechnology industry. Reflecting their polysaccharide substrates, LPMOs have been discovered by association with other carbohydrate-active enzymes and domains, but there is no chemical reason to suggest that the substrate range might be limited to sugar substrates. Here, we pioneer a new approach to lytic polymer oxygenase discovery. We unveil four potential new polymer degrading metal oxygenases, for domains implicated in fungal pathogenicity (on major crop plants and insects), and from plastic and hydrocarbon degrading organisms. The research will dissect these enzymes, focussing on their metal chemistry and application for the degradation and bioremediation of plastics and other hydrocarbons, and on their essential roles in fungal pathogenesis. The latter includes societally-damaging destruction of major food crops (rice, wheat etc) but also beneficial roles in insect suppression (these organisms are deployed as anti-malarials, for example). Like their polysaccharide-active progenitors, LPMOs active on non-polysaccharide polymer oxygenases also have the potential to be a disruptive enzyme class in hydrocarbon degradation, meeting unmet societal needs whilst unveiling powerful new metal chemistries.

Summary

Enzymes are nature's catalysts; they speed up chemical reactions which otherwise would take too long to be useful. Such is the power of enzymes to do this, that they have been utilised in very many applications. For instance, modern washing powders contain enzymes that breakdown the stains on clothes, but do this at temperatures which mean that washing can be done at a low temperature, saving energy. Another example is where enzymes are used in pregnancy testing kits to deliver highly accurate and rapid results. Despite the great advances in enzyme technology however, there is a gap in our understanding. This gap comes when an enzyme has to react with a solid substrate, say plastic or biomass. Here the substrate is so large that it cannot be 'wrapped-up' by the enzyme (as normal enzymes do when the substrate enters into the so-called active site of the enzyme). This inability to wrap-up a substrate detracts from some of the power of enzymes to speed up reactions by distorting and bending the shape of substrates such that they become reactive. This gap is serious, as there are many solid substrates which humankind would like to breakdown using enzymes. These include waste plant matter (that could be turned into fuel for instance) or waste plastics (which currently contaminate our oceans). This project is focussed on a recently discovered class of enzymes called lytic polysaccharide monooxygenases (LPMOs), which have been shown to breakdown cellulose (plant matter) which is an highly unreactive solid substrate. The power of LPMOs to catalyse this reaction is extraordinary, and is now posing new questions on how biology uses enzymes to breakdown solid matter. We seek to investigate the range of substrates that can be broken down by completely new classes of LPMOs that we have found using a technique called genome mining. We will isolate and study these enzymes in great detail, trying to understanding their chemical features and-most importantly-see if we can turn their properties to destroy solid matter towards societal good, in this case whether we can use these new LPMOs in insect control where they can be employed to breakdown the cuticles of mosquitoes.

Committee	Research Committee D (Molecules, cells and industrial biotechnology)
Research Topics	Industrial Biotechnology, Structural Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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