Frances Arnold wins Nobel Prize for Chemistry: Gevo, Provivi co-founder honored for directed evolution technology

In Sweden, the Royal Swedish Academy of Sciences awarded the Nobel Prize in Chemistry 2018 with one half to Frances H. Arnold,  Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry, at Caltech “for the directed evolution of enzymes”

It’s essentially a technology originally known as the Staggered Extension Process, or StEP. It’s an iterative, molecular technique that causes fragile, garden-variety proteins to evolve into usable chemical catalysts and drugs. 

Dr. Arnold is the co-founder Gevo and Provivi — technologies which spun out of her lab, and she continues to serve on the Provivi board of directors. Directed evolution technology, which was developed in her lab, was licensed originally to Maxygen and was ultimately spun out into Codexis, which continues to use the technology as its core. She also at various times served on the scientific advisory boards of Genomatica, Amyris, Mascoma, Fluidigm, and Codexis.

The directed evolution technology

Back in 1999, Maxygen obtained an exclusive worldwide license from the CalTech for the StEP.

What does it do? As Maxygen observed back in ’99, “it improves the performance and extends the utility of enzymes and proteins. At the organism level, scientists have tried to induce the evolution of hardy microorganisms and proteins simply by subjecting organisms to harsh chemical conditions or temperature extremes and growing whatever organisms survived. Sometimes it worked, most often it did not. 

An early and very successful example of directed evolution was carried out by Arnold to produce an industrially viable enzyme that hydrolyzes a para-nitrobenzyl ester of an antibiotic By applying sequential generations of random mutagenesis, recombination, and screening, the enzyme’s catalytic efficiency was increased more than 100-fold. While yielding a powerful new catalyst for important synthetic reactions, this work demonstrated that enzymes can acquire capabilities not found in naturally occurring organisms. It also showed that these capabilities may be conferred without conventional breeding or rational protein design.

The practical applications

As Codexis observes, “in the right hands, the power of engineered proteins to solve 21st century problems in pharmaceutical, biotherapeutic, food & beverage and other industries is almost unimaginable.

By speeding up and directing the evolution of proteins, we can potentially manufacture drugs more affordably; treat diseases more effectively with new biologic therapeutics; detect cancer before tumors develop; create healthier foods less expensively; and impact a wide array of industrial markets with improved enzymes and proteins.

More about Codexis, Gevo and Provivi

Proteins and Synthetic Biology: The Digest’s Multi-Slide Guide to Codexis

Plans for Luverne: The Digest’s 2018 Multi-Slide Guide to Gevo

I’ll Never Find Another You: Provivi’s protecting crops by confusing pests in their search for romance

The other Nobel Laureates in this cycle.

The other half was given jointly to George P. Smith, University of Missouri, Columbia, USA and Sir Gregory P. Winter, MRC Laboratory of Molecular Biology, Cambridge, UK “for the phage display of peptides and antibodies”.

The Nobel Committee wrote

The power of evolution is revealed through the diversity of life. The 2018 Nobel Laureates in Chemistry have taken control of evolution and used it for purposes that bring the greatest benefit to humankind. Enzymes produced through directed evolution are used to manufacture everything from biofuels to pharmaceuticals. Antibodies evolved using a method called phage display can combat autoimmune diseases and in some cases cure metastatic cancer.

Since the first seeds of life arose around 3.7 billion years ago, almost every crevice on Earth has filled with different organisms. Life has spread to hot springs, deep oceans and dry deserts, all because evolution has solved a number of chemical problems. Life’s chemical tools – proteins – have been optimised, changed and renewed, creating incredible diversity.

This year’s Nobel Laureates in Chemistry have been inspired by the power of evolution and used the same principles – genetic change and selection – to develop proteins that solve mankind’s chemical problems.

One half of this year’s Nobel Prize in Chemistry is awarded to Frances H. Arnold. In 1993, she conducted the first directed evolution of enzymes, which are proteins that catalyse chemical reactions. Since then, she has refined the methods that are now routinely used to develop new catalysts. The uses of Frances Arnold’s enzymes include more environmentally friendly manufacturing of chemical substances, such as pharmaceuticals, and the production of renewable fuels for a greener transport sector.

The other half of this year’s Nobel Prize in Chemistry is shared by George P. Smith and Sir Gregory P. Winter. In 1985, George Smith developed an elegant method known as phage display, where a bacteriophage – a virus that infects bacteria – can be used to evolve new proteins. Gregory Winter used phage display for the directed evolution of antibodies, with the aim of producing new pharmaceuticals. The first one based on this method, adalimumab, was approved in 2002 and is used for rheumatoid arthritis, psoriasis and inflammatory bowel diseases. Since then, phage display has produced anti-bodies that can neutralise toxins, counteract autoimmune diseases and cure metastatic cancer.

We are in the early days of directed evolution’s revolution which, in many different ways, is bringing and will bring the greatest benefit to humankind.

Reaction from Industry

Gevo CEO Patrick R. Gruber said “This award is well deserved. Frances has been a leader in the development of enzymes.  Gevo has been the beneficiary of her good work.  She, with her research group, developed some of the critical enzymes needed for Gevo’s biological pathway to produce renewable resource-based isobutanol.  Her work helped to establish Gevo as a leader in renewable resource based chemicals and fuels.  We congratulate her on her Nobel Prize, and for co-founding Gevo.”

Prize amount

9 million Swedish krona, (around $1 million) with one half to Frances Arnold and the other half to be shared between George Smith and Gregory Winter.

Digest notes

Dr. Arnold had won almost everything you could win up to the time of this well-deserved Nobel.

To name just a few, she was inducted into the US National Academies of Science, Medicine and Engineering, the American Academy of Arts and Sciences and the National Inventors Hall of Fame. Her awards include the Charles Stark Draper Prize of the National Academy of Engineering, the Millennium Technology Prize, the National Academy of Sciences’ Sackler Prize in Convergence Research, and the US National Medal of Technology and Innovation. She also chairs the Advisory Panel of the David and Lucile Packard Foundation Fellowships in Science and Engineering.

More on the story, here.