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

Informazioni relative al progetto

METENZ

ID dell’accordo di sovvenzione: 656455

DOI

10.3030/656455

Progetto concluso il 9 Gennaio 2018

Data della firma CE 13 Aprile 2015

Data di avvio 1 Aprile 2015

Data di completamento 31 Marzo 2018

Finanziato da

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Costo totale

€ 251 857,80

Contributo UE

€ 251 857,80

Coordinato da

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.)

Periodo di rendicontazione: 2017-04-01 al 2018-03-31

Sintesi del contesto e degli obiettivi generali del progetto

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.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

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.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

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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