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

Información del proyecto

METENZ

Identificador del acuerdo de subvención: 656455

DOI

10.3030/656455

Proyecto finalizado el 9 Enero 2018

Fecha de la firma de la CE 13 Abril 2015

Fecha de inicio 1 Abril 2015

Fecha de finalización 31 Marzo 2018

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 251 857,80

Aportación de la UE

€ 251 857,80

Coordinado por

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.)

Período documentado: 2017-04-01 hasta 2018-03-31

Resumen del contexto y de los objetivos generales del proyecto

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.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

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.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

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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