By Kevin Bailey, Technical Analyst
This year’s Nobel Prize in Chemistry has been awarded to three scientists for their work harnessing the power of evolution to develop new proteins used in drugs and medical treatments. The scientists, Frances Arnold and George P Smith, and Gregory Winter pioneered the work in the 1980’s and 1990’s.
Directed evolution mimics the process of natural selection by allowing researchers to steer proteins or nucleic acids towards user-defined functionality. This process involves repeated rounds of random gene library generation (mutagenesis) followed by expression of genes in a suitable host. The property of interest is then screened for, either in living cells or in vitro, in the libraries of variant enzymes produced, isolating library members with the desired function (selection).
Winter and Smith’s contribution to directed evolution was the development of a technique, phage display, where a specific protein’s genetic cone is artificially inserted into a bacteriophage’s coat protein gene, causing the protein to be displayed on the outside of the bacteriophage. This work enabled in vitro screening of ligands for proteins and other macromolecules. Smith first reported phage display in 1985, and Winter developed the technique further for the purpose of finding novel therapeutics. Later work by Arnold in 1993 used this principle to engineer enzymes to perform particular functions, initially focussing on the enzyme subtilisin E.
Directed evolution is therefore a powerful strategy for improving the characteristics of enzymes in a targeted manner. The generation of large variant libraries genes, together with high-throughput screens that select for specific properties of an enzyme allow the optimisation of biocatalysts for specific applications, replacing traditional chemical processes used to generate certain products, such as pharmaceutical and agrochemical building blocks, fine and bulk chemicals and biofuels.