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Purposing de novo protein scaffolds for the Heck reaction

Project description

Enzyme design to clean up synthetic chemistry reactions

There is an overall consensus that greenhouse gas emissions threaten the earth's ecosystem and necessitate immediate mitigating strategies. The EU-funded DENOPHECK project proposes to develop, cleaner and lower-energy reactions through the modification of the most studied coupling reaction recognised by a Nobel prize, the Heck reaction. The Heck reaction uses palladium to facilitate bond formation between carbon atoms and has revolutionised synthetic chemistry. DENOPHECK will undertake de novo protein design to generate novel Heck reaction enzymes that function at ambient temperatures and demonstrate optimal stereoselectivity. The project's findings will advance the chemical methodologies currently used for the synthesis of agrochemical, pharmaceutical and fine chemicals and contribute towards a cleaner planet.

Objective

The overall aim of this fellowship is to develop an enzymes that catalyses the Heck reaction using de novo proteins.

We now live in an age where the consequences of the emissions of greenhouse gases are having observable, detrimental effects on our planet’s ecosystem. Therefore, the need to develop non-toxic, cleaner and lower energy reactions is essential. Palladium(0)-catalysed cross-coupling reactions are a powerful method for generating carbon-carbon and carbon-heteroatom bonds, leading to their extensive use in academia and industry. Among all cross-coupling reactions, it can be argued that the Heck reaction is one of the greenest because the reagents are not prefunctionalised with metals, boron or silicon. Furthermore, it has been demonstrated that the Heck reaction can be performed in water, although truly catalytic examples to date require temperatures up to 140 °C and often more reactive and expensive aryl bromide and aryl iodide reagents.

De novo protein design, the selection of an amino-acid sequence that will fold to a desired protein structure, is a newly established field. Successful designs have furnished a diverse range of protein structures. In contrast to most natural proteins, de novo proteins are well understood, have high thermal stability and are characterised to atomic detail.

Dr Rhys, under the supervision of Prof Höcker & Prof Weber, proposes to purpose a range of de novo proteins to bind artificial co-factors to develop truly de novo Heckase enzymes. Functional enzymes will be optimised using well-established rational design and directed-evolution techniques.

The development of an optimised Heckase could overcome existing challenges to produce an ambient temperature, stereoselective, water-soluble Heck catalyst.

Coordinator

UNIVERSITAT BAYREUTH
Net EU contribution
€ 162 806,40
Address
UNIVERSITATSSTRASSE 30
95447 Bayreuth
Germany

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Region
Bayern Oberfranken Bayreuth, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 162 806,40