CORDIS - EU research results
CORDIS

Enzyme design and engineering by implementation of non-canonical amino acids in protein scaffolds

Project description

Enzymes reengineered for a novel catalyst design

Increasing the speed and energetic efficiency with which reactions occur is critical to numerous processes in nature, industry and medicine. Specialised molecules called catalysts do the job. In nature, the majority of catalysts are enzymes, complex proteins made of amino acid sequences. Non-enzymatic catalysts are also found in nature and are particularly prevalent in industrial processes. However, they typically require high temperatures and large concentrations to perform satisfactorily. Thiazolium salts have long been used as catalysts in organic chemistry and THIAZOLIUMenzyme is developing a way to get the best of both worlds. Incorporating thiazolium amino acids into an enzyme, the team plans to deliver a greener catalyst for industrial applications and a novel enzyme for medical use.

Objective

The design of enzymatic catalysts and protein therapeutics with tailored, new-to-nature properties is a long-standing goal in enzymology and cell biology. Nature generally uses 20 amino acids as building blocks for protein synthesis. However, this portfolio limits the options for engineering proteins with ‘un-natural’ activities. Recent developments in the expansion of the genetic code have the potential to revolutionise the design of novel enzymes; by reprogramming the genetic code, we could convey novel functionality into proteins and extend their properties. This project aims at incorporating thiazolium amino acids into the active site of a promiscuous and highly evolvable de novo enzyme, namely the RA95 (retro)-aldolase, for orchestrating organocatalytic transformations of clinical and industrial interest. Such reactions, conventionally mediated by non-enzymatic, small molecule N-heterocyclic carbene (NHC) catalysts require high temperature and catalyst loading. An engineered enzyme with the ability to catalyse such chemistry may overcome the drawbacks of these abiological catalysts, serving as a ‘greener’ biocatalytic alternative, and also perform the desired reactions in cells for medicinal purposes. This initiative will pave the way for development of general strategies for creating enzymes with unique properties and provide a tool-box for efficient, environmentally-friendly and bioorthogonal organocatalysed reactions. It is anticipated that the generated artificial biocatalysts will have attractive applications in research, medicine and industry.

Coordinator

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Net EU contribution
€ 191 149,44
Address
Raemistrasse 101
8092 Zuerich
Switzerland

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Region
Schweiz/Suisse/Svizzera Zürich Zürich
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 191 149,44