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Teaching Lytic Polysaccharide Monooxygenases to do Cytochrome P450 Catalysis

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.

Coordinator

NORGES MILJO-OG BIOVITENSKAPLIGE UNIVERSITET
Net EU contribution
€ 1 164 322,50
Address
Universitetstunet 3
1433 As
Norway

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Region
Norge Oslo og Viken Viken
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00

Participants (3)

INSTYTUT KATALIZY I FIZYKOCHEMII POWIERZCHNI IM. JERZEGO HABERA POLSKA AKADEMIA NAUK
Poland
Net EU contribution
€ 367 750,00
Address
Ul. Niezapominajek 8
30239 Krakow

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Region
Makroregion południowy Małopolskie Miasto Kraków
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
POLITECHNIKA SLASKA
Poland
Net EU contribution
€ 685 750,00
Address
Ul. Akademicka 2a
44-100 Gliwice

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Region
Makroregion południowy Śląskie Katowicki
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
TECHNISCHE UNIVERSITAET GRAZ
Austria
Net EU contribution
€ 781 950,00
Address
Rechbauerstrasse 12
8010 Graz

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Region
Südösterreich Steiermark Graz
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00