Speeding up biomolecular evolution

April 11, 2011

Scientists at Harvard University have harnessed the ability of fast-replicating bacterial viruses to accelerate the evolution of biomolecules in the laboratory.

The research exploited the continuous culture and selection of bacterial viruses to enable the continuous directed evolution of proteins and nucleic acids. This phage-assisted continuous evolution (PACE) is roughly 100 times faster than conventional laboratory evolution, and far less labor-intensive for scientists.

The scientists achieved up to 60 rounds of protein evolution every 24 hours by linking laboratory evolution to the life cycle of a virus that infects bacteria. The PACE system uses E. coli host cells to produce the resulting proteins, to serve as factories for phage production, and to perform the key selection step that allows phage-carrying genes encoding desired molecules to flourish.

In three protein evolution experiments, PACE was able to generate an enzyme with a new target activity within a week, achieving up to 200 rounds of protein evolution during that time. Conventional laboratory evolution methods would require years to complete this many rounds of evolution, the researchers say.

The work could ultimately allow for tailoring custom pharmaceuticals and research tools from lab-grown proteins, nucleic acids, and other such compounds, suggests Professor David R. Liu.

Ref.: Jacob C. Carlson & David R. Liu et al., A system for the continuous directed evolution of biomolecules, April 10 online edition, Nature