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A helping hand for protein evolution

European research is harnessing Darwinian evolution (selection of the fittest) in the laboratory. The scientists are creating and screening libraries of proteins for new enzymes and antibodies to use in the fine chemical, pharmaceutical, consumer care and food/feed industries.
A helping hand for protein evolution
Directed evolution is used in protein engineering to evolve nucleic acids or proteins for a pre-defined purpose. Mimicking the process of natural selection, the method involves 'mutating' or changing a protein and screening the resulting molecules for usefulness.

The 'European network on directed evolution of functional proteins' (ENEFP) project is comprised of academic and industrial groups. The laboratories are equipped with skilled staff and state-of-the-art equipment. Tools include those for mechanistic enzymology and a technology platform including phage display, in vitro compartmentalisation, ribosome display, selective protein labelling and high-throughput screening in microfluidic droplets.

Completed in 2012, the four-year project has worked on enzymes for therapeutic purposes. These include beta-lactamase for antibiotics research, cytosolic sulphotransferases as well as a therapeutic lipase.

For directed evolution, the team have developed tools to facilitate and guide the direction of the changes in proteins. Many enzymes that are remarkably specific can catalyse other lesser reactions that are under neutral selection. These so-called promiscuous enzymes are also being studied by ENEFP — this considerably widens the net for discovery of useful proteins.

Other equipment and work in progress include a new protein display system and a ratiometric fluorescent biosensor along with a neurotransmitter (g-aminobutyric acid). On the enzyme front, the team are investigating the optimisation of a lipase for expression in other hosts, the discovery of enzymes that remove amino groups to create non-natural amino acids and the development of esterases with higher stereoselectivity.

ENEFP members have also devised a comprehensive training programme for young researchers. This includes experimental techniques and a summer school on protein engineering, as well as lectures and workshops on entrepreneurship and industry.

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