ASTADAN, Chantelle Gayle B.

BS ChE 5

AUG 2016
Ch E 514A

8:30 9:30 TTHS

PA1

DIRECTED EVOLUTION
Frances Arnold, 59, won the prize for her discoveries that launched a field known as directed evolution,
according to a statement issued by Technology Academy Finland, the organization that awards the prize.
What is directed evolution?
A technology that allows us to reliably create improved proteins for a wide range of applications. Just as
farmers and breeders have used artificial selection processes over thousands of years to create higheryielding crops or pets that please us, we can direct the evolution of proteins to perform better in
applications, from laundry detergents to green chemistry.
Modern methods of DNA manipulation allow us to make iterations of mutations and artificial selection on
a gene rather than in an organism, and to shorten the generation time to a few days. That way we can
accumulate beneficial mutations in the gene that encodes the protein, making it better and better until it
meets our needs.
Directed evolution circumvents our profound ignorance of how a protein's sequence encodes its function
by using iterative rounds of random mutation and artificial selection to discover new and useful proteins.
Proteins can be tuned to adapt to new functions or environments by simple adaptive walks involving
small numbers of mutations. Directed evolution studies have shown how rapidly some proteins can
evolve under strong selection pressures and, because the entire 'fossil record' of evolutionary
intermediates is available for detailed study, they have provided new insight into the relationship between
sequence and function. Directed evolution has also shown how mutations that are functionally neutral can
set the stage for further adaptation.
How does directed evolution differ from evolution as we commonly think of it?
It differs from natural evolution in that it is directed by the researcher. Mutations are directed (by me) to a
specific gene, and since the researcher has a goal in mind, it is also directed in that sense.

How is directed evolution being used commercially?

Directed evolution has had big impact in the fields of drug synthesis. Many popular drugs, including the
cholesterol-lowering drugs simvastatin and atorvastatin, have been developed with the help of directed
evolution. The same is true for making consumer products (key ingredients for creams, laundry
detergents, animal and human nutrition products and many more) and for making non-ethanol fuels like
isobutanol from renewable plant resources.
What are the biggest advances that have come from the commercial application of directed
evolution?
My former student and one of the first people to use directed evolution, Dr. Jeffrey Moore, and his
collaborators figured out how to manufacture the diabetes drug Januvia using an evolved enzyme. Their
process replaces chemical methods that were far from optimal, lowering the cost of the drug and
especially the waste products. Their process won many awards, including the Presidents Green
Chemistry Challenge.
Many companies now incorporate enzyme catalysts into their processes. More will do so as we move to
greater sustainability in manufacturing.
A number of companies that make fuels and chemicals from renewable resources have used DE to
optimize enzymes. Enzymes optimized by directed evolution are being used to make nutritional products
for humans and animals, fuel from biomass and to test new drugs for toxicity. They are being used
directly to treat human disease.
Engineered enzymes are used in everything from DNA sequencing to glucose sensors for diabetes,
laundry detergents and food processing.
What do you foresee for directed evolution in the future?
The wonderful thing about directed evolution is that it is both simple and general. Because the technology
is accessible, it can be implemented in any laboratory. It opened up a new way for people to look at the
inventions of the biological world and fit them into their own creations.
So many clever people all over the world have taken this technology and done all manner of brilliant
things with it, things I would never have thought of. This will continue in the future.