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Prenylated-flavins: Application and Biochemistry

Objective

Our group has recently discovered a new type of cofactor: a prenylated-flavin that has azomethine ylide properties. This cofactor is an integral part of the widespread ubiD/ubiX system. The latter is implicated in the non-oxidative reversible decarboxylation of aromatic substrates, and plays a pivotal role in bacterial ubiquinone biosynthesis or microbial biodegradation of aromatic compounds. We established UbiX acts as a novel flavin prenyltransferase, linking a dimethylallyl moiety to the flavin N5 and C6 atoms. Formation of the holo-UbiD enzyme involves oxidative maturation of the new cofactor, creating the novel azomethine ylide moiety. The dipolarophile substrate binds directly above the azomethine ylide group, and our data strongly suggests 1,3-dipolar cycloaddition chemistry supports reversible decarboxylation in these enzymes. While 1,3-dipolar cycloaddition is commonly used in organic chemistry, this presents the first example of an enzymatic 1,3-dipolar cycloaddition reaction. Our model for UbiD catalysis hints at new routes in alkene hydrocarbon production or aryl (de)carboxylation.

The current application builds ambitiously on these results and takes the project altogether to another level: we seek to investigate structure/function of relationships of the wider UbiD family, ultimately including the multi-subunit enzymes that couple ATP-hydrolysis to benzene or naphthalene carboxylation. Furthermore, we will explore and harness the unusual properties of the prenylated flavin, through targeted evolution of (monoxygenase) flavoenzymes to create artificial prFMN-dependent self-sufficient monoxygenases. Our approach seeks to harness both the UbiD and the artificial prFMN-dependent enzymes in novel green routes to commodity chemicals.

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Topic(s)

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Funding Scheme

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ERC-ADG - Advanced Grant

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Call for proposal

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(opens in new window) ERC-2015-AdG

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Host institution

THE UNIVERSITY OF MANCHESTER
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 494 328,75
Address
OXFORD ROAD
M13 9PL Manchester
United Kingdom

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Region
North West (England) Greater Manchester Manchester
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 494 328,75

Beneficiaries (1)

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