Directed evolution could produce life-saving therapies

Proseeker is the name of a new computational tool that mimics the processes of natural selection, producing proteins that can be used for a range of medicinal and household uses.

The enzymes in your laundry detergent, the insulin in your diabetes medication or the antibodies used in cancer therapy are currently made in the laboratory using a painstaking process called directed evolution.

Laboratory evolution mimics natural evolution by making mutations in naturally-sourced proteins and selecting the best mutants, to be mutated and selected again, in a time-intensive and laborious process that creates useful proteins.

Scientists at the ARC Centre of Excellence in Synthetic Biology have now discovered a way to perform the entire process of directed evolution using a computer. It can reduce the time required from many months or even years to just days.

The team was led by Professor Oliver Rackham, Curtin University, in collaboration with Professor Aleksandra Filipovska, the University of Western Australia, and is based at the Harry Perkins Institute of Medical Research in Perth, Western Australia.

To prove how useful this process could be they took a protein with no function at all and gave it the ability to bind DNA.

‘Proteins that bind DNA are currently revolutionising the field of gene therapy where scientists are using them to reverse disease-causing mutations,’ says Professor Rackham. ‘So this could be of great use in the future.

‘Reconstituting the entire process of directed evolution represents a radical advance for the field.’

The work is described in a new paper in Nature Chemical Biology.

Publication: Samuel A. Raven, et al., In silico evolution of nucleic acid-binding proteins from a nonfunctional scaffold, Nature (2022). DOI: s41589-022-00967-y

Original story source: Curtin University News