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.
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. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural scienceschemical sciencesorganic chemistryhydrocarbons
- natural scienceschemical sciencescatalysis
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Keywords
Programme(s)
Topic(s)
Funding Scheme
ERC-ADG - Advanced GrantHost institution
M13 9PL Manchester
United Kingdom