Dr. Frances Arnold: Looking for Novelty through Directed Evolution

Contributor III
0 0 3,374

Catalysis, the process of reducing a reaction’s energy requirement through use of a catalyzing agent, is a standard design principle of green chemistry. Yet many of the catalysts that chemists use are made out of rare metals like platinum. Figuring out how to do catalysis without using unsustainable catalysts is a priority to green chemists and companies seeking to find better, more efficient, cheaper, and ecological pathways to produce their products. One inspiration for solving such a problem has been nature.

Enzymes, a type of protein, are nature’s catalysts, working within cells to speed up reactions of all kinds. For example, enzymes in our digestive tract help break down food so that we can more rapidly benefit from it. But how can enzymes help chemists? Well, what if enzymes could be manipulated to catalyze the industrial reactions industry performs, such as creating a drug molecule or biofuel?

Enter Dr. Frances Arnold, professor of chemical engineering, bioengineering and biochemistry at Caltech and director of the Donna and Benjamin M. Rosen Bioengineering Center. Arnold has developed a method of protein engineering called directed evolution. The basic process involves encouraging random mutations in the gene sequence for a protein of interest, such as an enzyme catalyst. The genes are introduced in bacteria or yeast, which produce the mutant enzymes.  As the bacteria express the mutated genes, the resulting proteins are screened for favorable behaviors. Genes responsible for favorable traits are then extracted and reinserted into the next evolutionary round.


Credit: Joe Lertola, Bryan Christie Design

The goal of the process is to produce an enzyme that works in a way not found in nature. “I’m most excited about creating enzymes to catalyze reactions that nature never cared about or discovered,” says Professor Arnold. “I want to evolve chemical novelty, in the form of whole new enzymes.”

Over the past two years, Arnold has published 10 papers on this subject, finding enzymatic approaches to reactions that previously only chemists had been able to produce. But finding novelty through evolution is not always easy.

It’s clear that nature has the capacity to produce new catalytic activities, for example degrading synthetic pesticides sprayed on crops, but it’s far from clear how nature creates these new catalytic pathways. Cracking this code is a challenge that could open up opportunities to replace many of the reactions chemists do with more favorable, biological reactions. Breaking down the walls between traditional catalysis and biocatalysis will maximize the creative potential of both fields.

In Arnold’s research group at Caltech, students of molecular biology, biochemistry, bioengineering and chemistry work together. “I know chemists who feel that biology is the big frontier for them,” says Arnold. “They can apply their more traditional chemical knowledge to identifying new opportunities for biological synthesis.”

Young chemists know that the field is changing and more jobs are opening in these cross-disciplinary areas. According to a MarketsandMarkets Report released in February, the market for biocatalysts is projected to grow at 5.5% per year and reach 11.94 kilo tons by 2019. Driven by technological advances, biocatalysis is particularly strong in Europe and the United States, where biocatalysts are used in laundry detergent, the food and beverage industry, the specialty chemicals and pharmaceuticals industries, and increasingly in the production of biofuels. Many start-ups are employing these methods, especially in the production of biofuels and specialty chemicals. Arnold herself has founded two companies, Gevo, Inc., which uses her methodology to create the biofuel isobutanol, and Provivi, a start-up that is developing new products for crop protection.

Large companies are also embracing the developing capabilities of biochemistry. In 2010 Merck, in partnership with Codexis, developed an enzymatic process for producing the active ingredient in Januvia™, a drug used in the treatment of type 2 diabetes. The new process replaced a rare metal rhodium catalyst and won the team a Presidential Green Chemistry Challenge Award from the EPA that same year.

Professor Arnold will be keynoting at the 19th Annual Green Chemistry & Engineering Conference this July 14-16 in North Bethesda, Maryland where she will talk about chemical novelty and the opportunities for green chemists and engineers in this field.

“Doing great science is hard, but doing great science that has an impact is even harder,” says Arnold. “So if you like challenges, try to do that.”

Arnold has received numerous honors, including induction into the National Inventors Hall of Fame (2014), the ENI Prize in Renewable Energy (2013), the National Medal of Technology and Innovation (2011) and the Draper Prize of the National Academy of Engineering (2011). She has been elected to membership in all three US National Academies, of Science, Medicine, and Engineering. Among other activities, Prof. Arnold chairs the Advisory Panel of the Packard Fellowships in Science and Engineering and serves as a judge for the Queen Elizabeth Prize in Engineering.  Arnold holds more than 40 US patents and has served on the science advisory boards of numerous companies. She co-founded Gevo, Inc. in 2005 to make fuels and chemicals from renewable resources and Provivi in 2013 to develop new products for crop protection.

“The Nexus Blog” is a sister publication of “The Nexus” newsletter. To sign up for the newsletter, please email gci@acs.org, or if you have an ACS ID, login to your email preferences and select “The Nexus” to subscribe.

To read other posts, go to Green Chemistry: The Nexus Blog home.