To develop a novel class of metalloenzymes for application in novel asymmetric C-H activation chemistry.

Informations projet

METENZ

N° de convention de subvention: 656455

DOI

10.3030/656455

Projet clôturé le 9 Janvier 2018

Date de signature de la CE 13 Avril 2015

Date de début 1 Avril 2015

Date de fin 31 Mars 2018

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 251 857,80

Contribution de l’UE

€ 251 857,80

Coordonné par

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
United Kingdom

Periodic Reporting for period 2 - METENZ (To develop a novel class of metalloenzymes for application in novel asymmetric C-H activation chemistry.)

Période du rapport: 2017-04-01 au 2018-03-31

Résumé du contexte et des objectifs généraux du projet

Chemical catalysis is used to take cheap, raw chemical feedstocks and convert them efficiently into complex, high value, chemicals. During the outgoing phase of my Marie-Curie Fellowship I work on the development of novel artificial metalloenzymes for chemical catalysis. Artificial metalloenzymes consists of a transition metal embedded in a protein scaffold host. Here the transition metal controls the core reactivity of the catalyst and the surrounding protein host can influence aspects of the reaction such as rate and selectivity. We believe that an optimised artificial metalloenzyme can be used to generate chemicals that have been previously inaccessible by conventional transition metal catalysis. This is a relatively new area of catalysis and only a small number of proteins have been used to host transition metals to create metalloenzymes. Our first objective is to create a metalloenzymes based on novel protein host that displays unique and improved properties over previously developed artificial metalloenzymes. Our second objective is focused on the development of a technology for the optimisation of metalloenzyme catalyst. The proteins that are used to host transition metals are often difficult to synthesis, and with the application of genetic techniques, as many different mutants of each protein are available (>1 million). Making 1 million different proteins to use as metalloenzymes is not practical. We are developing technology for the high-throughput synthesis and reaction screening of a library of metalloenzymes. This technology will hopefully allow for the identification of very active artificial metalloenzymes.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Initially I focused on developing novel artificial metalloenzymes based on the novel protein scaffolds. Although many proteins were found not to be applicable for use as artificial metalloenzymes I found that the recently described monomeric streptavidin protein could be used to host a rhodium catalyst. This artificial metalloenzyme was capable of catalysing a range of reactions that made drug like molecules. I also worked towards developing a method that would allow for the analysis of >1 million different artificial metalloenzyme catalysts to select a highly efficient catalyst.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

A novel metalloenzyme based on monomeric streptavidin was developed as shown to catalyse the formation of molecules previously difficulties to access. After publication of these results we may expect to see this technology, or variants of it, adopted by industry to synthesise useful chemicals. Areas of industry that would use this technology include the pharmaceutical sector and agrochemical sector. Although results are preliminary, a method for the high-throughput screening of metalloenzymes would revolutionise the field and streamline the development of new artificial metalloenzyme catalysts and thus novel chemical reactions.

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