Project description
Engineered LPMO could boost hydrocarbon reactions
Lytic polysaccharide monooxygenases (LPMOs) and cytochromes P450 (CYPs) are copper enzymes that catalyse the regio- and stereospecific oxidation of non-activated hydrocarbons. Such reactions are central to biotechnology, enabling the creation of valuable products such as second-generation bioethanol and value-added chemicals. To overcome the drawbacks related to CYP use, the EU-funded NewCat project aims to develop a new type of catalyst – engineered LPMOs – that can perform the same type of reactions. LPMOs are small and rigid water-soluble proteins that are easy to produce in large scale.
Objective
"Lytic polysaccharide monooxygenases (LPMO) and cytochrome P450 (CYP) are copper- and iron-dependent, respectively,
enzymatic systems that perform regio- and stereospecific oxidation of non-activated hydrocarbons in Nature. To control such
reactions in modern industry and biotechnology is of utmost importance in creating products of value such as secondgeneration
bioethanol and products of value for i.e. the pharmaceutical industry. Due to the major drawbacks of using CYPs,
including their partially membrane bound nature and the requirement of a reductase in combination with reducing agents
such as NAD(P)H to transfer electrons to the active site for oxygen activation, it is highly desirable to develop new type of
catalyst that can perform the same type of reactions. An attractive alternative strategy is to engineer LPMOs to perform CYP
catalysis. LPMOs are small, robust, easy to produce in large scale, and rigid water-soluble proteins with a plethora of
electron donors. The extended, flat LPMO surface, with huge natural sequence variation and thus, likely, mutability, provides
a fantastic scaffold for engineering access to the active site as well as substrate affinity. We propose to use LPMOs
engineered to accommodate typical CYP substrates and immobilize this on solid supports to provide confinement necessary
in bringing the oxygen species together with the C-H bond to be oxidized in a tailored, ""closed"" environment. Moreover, the
rate of LPMO catalysis can be greatly enhanced compared to traditional CYP catalysis by the addition H2O2 in the presence
of low, priming concentrations of an external reductant to achieve efficiency constants (kcat/Km) in the order of 106 M-1s-1,
which is typical for peroxygenases. The proposed ground-breaking research fits excellently well with the work program
""Future and Emerging Technologies"" where the goal is to challenge current thinking."
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. This project's classification has been validated by the project's team.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. This project's classification has been validated by the project's team.
Keywords
Programme(s)
Call for proposal
(opens in new window) HORIZON-EIC-2021-PATHFINDEROPEN-01
See other projects for this callFunding Scheme
HORIZON-EIC - HORIZON EIC GrantsCoordinator
1433 As
Norway