Nobel Chemistry at UC Berkeley Ph.D. Frances Arnold

When Frances Arnold first arrived at the University of Berkeley in 1980, as a graduate student, she focused on biofuels – a promising new technology and, for Arnold, a way to benefit humanity by removing the company from fossil fuels.

But falling oil prices and President Ronald Reagan have destroyed that dream.

"Once oil prices have fallen, biofuels have no future, and Reagan has virtually destroyed all research funding," said Harvey Blanch, Ph.D. of Arnold. Consultant and Emeritus Professor of Chemical and Biomolecular Engineering. "This financing did not come back until about 2006, when the price of oil rose to over $ 100 a barrel."

This setback paved the way for a new vision – using evolution to rethink the enzymes to use in biotechnology – which earned Arnold the 2018 Nobel Prize in Chemistry today.

The Nobel Committee divided the price of chemistry. Half was awarded to Arnold, now professor at Caltech, "For the Directed Evolution of Enzymes", and the other half to George P. Smith and Sir Gregory P. Winter, for related work on " phage display ". Smith is at the University of Missouri, Columbia, and Winter at the MRC Molecular Biology Laboratory in Cambridge, UK.

"Frances' work has added new dimensions to protein chemistry and biotechnology," said Douglas Clark, Dean of the Berkeley College of Chemistry and friend of Arnold's. "Frances remains at the forefront of this fast-growing technology and shows vividly how exciting innovations can emerge from research at the crossroads of different fields."

After completing his undergraduate degree in mechanical engineering at Princeton in 1979, Arnold briefly worked at the Golden Solar Research Institute in Colorado before enrolling in the Berkeley Chemical Engineering Department. to work on biofuels with Blanch. His experience in mechanical engineering forced him to take all undergraduate courses in chemical engineering before he could undertake his graduate program. She completed the full program in 12 months.

"All the professors in my department regarded Frances as an extraordinary student because she was skilled in mathematical analysis, in the expression of creative ideas and in encyclopaedic knowledge of molecular biology," said Jeffrey Reimer, currently director. from the Department of Chemical and Biomolecular Engineering.

Biofuels to biotechnology

Blanch was working on biofuels for a period that he called "Biofuels 1.0" and, once the funding fell to zero, he also left for another search. Arnold is involved in biotechnology, through a Berkeley group called the Biotechnology Research Center, and ended up doing his PhD. work on affinity chromatography, a relatively new technique for accurately separating proteins based on their affinity for another molecule, such as an antibody. His 1985 thesis was entitled "Evolutionary Genius of Affinity Chromatography".

She worked for about 18 months as a postdoctoral fellow at Ignacio Tinoco, a chemist at the University of Berkeley, who studied the structure of RNA, or ribonucleic acid.

In 1986, Arnold set up his own laboratory at Caltech, where she began her work on the directed evolution of enzymes. She is soon appointed Assistant Professor. His work has had a major impact on the pharmaceutical industry.

"The concept is extremely intelligent and technically elegant execution: combining the power of evolution with the effectiveness of modern biochemical methods," Clark said. "The so-called directed evolution is now used worldwide, both in industry and in academia."

"Her own work was started by a group of people in a managed evolution, but she found very, very smart ways to do it, and then really took off, with applications in green chemistry and even some applications in the field of Biofuels, says Blanch. "Thanks to her many accomplishments with evolving enzymes, she has been able to show that she can do things that we did not expect and that we've never seen on Earth." before. "

The directed evolution, explained Blanch, is based on a simple premise: that the approach taken by nature to optimize biological function, namely natural selection, can be used in the laboratory to provide the same remarkable results .

"Arnold has shown that enzymes can be" reproduced "for behavior that may not be relevant in a natural context but is important for human uses," he said. "Rather than having to design a process that meets the requirements of an existing enzyme, directed evolution makes it possible to adapt the catalyst to optimal manufacturing conditions."

Arnold has developed iterative methods that mimic random mutagenesis and selection found in nature, as well as screening techniques to select for mutations with targeted properties.

"This technology has been particularly important for the emerging chemicals and fuels industry based on renewable resources," he added. "The creation of microorganisms to transform solar radiation or biomass into fuels and chemicals requires new biocatalysts and new metabolic pathways that do not exist in nature."

The number of industrial enzymes that have been developed by managed evolution continues to grow, Blanch noted. Arnold has notably developed esterases for the pharmaceutical industry, thermophilic enzymes, enantioselective syntheses for pharmaceuticals, insecticides and herbicides, as well as the biocatalytic synthesis of new natural products, such as carotenoids.

More recently, she has created unusual reactions between carbon and boron, and carbon and silicon, which is "rather fascinating because you start thinking about other life forms," ​​Blanch said.

According to a statement from Caltech, Arnold woke up this morning while she was in Dallas to attend a conference, but she immediately rescheduled her flight back to California.

"I am absolutely disappointed. I must understand that. It's not something I was waiting for, "she said.

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