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Evolved enzymes

Did you know that researchers can mimic evolution in the lab? Scientists at Victoria University in Wellington are mimicking evolution at the level of individual genes to improve enzymes for cancer treatment.

Evolution

Evolution is a gradual change in the traits of a population that occurs over time. Traits are characteristics of an organism, like size, strength and colour. Genes determine the traits an organism has. During evolution, genes that are associated with beneficial traits tend to predominate in a population.

Get information sheet: Factors that influence evolution

Selective breeding

For thousands of years, we have bred animals and plants for particular traits. This is called selective breeding. For example, we have bred all of our current dog species from wild dogs, by selecting for particular traits such as size, strength and shape. We have also bred new varieties of roses by selecting parent plants for traits such as colour and scent and crossbreeding them.

Selective breeding helps us keep or enhance certain traits in a population, and it can also help us to remove unwanted ones.

What if you wanted to make a new enzyme or protein, rather than a whole plant or animal?

Directed evolution

In David Ackerley’s lab at Victoria University, they are using a form of selective breeding to make enzymes with new or improved functions.

Instead of selecting for a trait in an organism, the researchers are selecting for a protein with a particular function. The process is called directed evolution. It is similar to evolution but happens over a much shorter time, because the process of evolution is directed at the one gene that codes for that protein.

Get information sheet: How to direct evolution

Evolving enzymes

Enzymes are proteins that catalyse a large range of chemical reactions in cells. Enzymes have many uses in industry, agriculture and medicine. For example, enzymes are used to remove stains from clothes, treat pollution or produce penicillin. However, the ideal enzyme for a particular use cannot always be found in nature.

Using directed evolution, scientists can improve the function of enzymes that occur naturally.

Get information sheet: Directed evolution makes useful enzymes

Evolved enzymes and cancer treatment

In New Zealand, a new cancer treatment is being developed that uses an evolved enzyme. The enzyme activates a prodrug, which releases a toxic metabolite, causing cells to die.

In David Ackerley’s lab, they are using directed evolution to make an enzyme that is more efficient at activating the prodrug. The most efficient enzyme they find will be used in this cancer treatment.

For this new cancer treatment, the patient is first given a prodrug. Then the enzyme is given to the patient in a viral vector. The viral vector delivers the enzyme only to cancer cells. The enzyme activates the prodrug, and a toxic metabolite is produced that kills the cancer cells. Because the viral vector is specific for cancer cells, healthy cells are unharmed. Also, because the enzyme is originally from bacteria, it is unlikely to have any other effects in human cells.

This cancer treatment is being developed in collaboration with researchers at the Maurice Wilkins Centre for Molecular Biodiscovery.

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