Frances H. Arnold

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Frances H. Arnold (2012)

Frances Hamilton Arnold (born July 25, 1956 in Pittsburgh , Pennsylvania ) is an American biochemist and chemical engineer. She is Professor of Chemical Engineering , Biochemistry, and Bioengineering at the California Institute of Technology (Caltech) and holds the Dick and Barbara Dickinson Professorship . She is considered a pioneer in the field of directed evolution in chemistry. In 2018 she was awarded the Nobel Prize in Chemistry for her achievements .

Life

Arnold grew up in a suburb of Pittsburgh , Pennsylvania as the daughter of nuclear engineer William Howard Arnold . She is the granddaughter of General William Howard Arnold . In her youth, she protested the Vietnam War , moved to Washington DC in rebellion against her parents' home, where she financed the high school herself by serving waiters at a jazz club and driving cabs, and was in South America to work on a solar energy project. She graduated from Princeton University with a bachelor's degree in aerospace engineering and mechanical engineering in 1979 and a PhD in chemical engineering from the University of California, Berkeley , in 1985 . Her dissertation was called Design and scale-up of affinity separations . From 1986 she was at Caltech.

plant

She is known as one of the pioneers in the use of directed evolution methods in the development of new proteins for e.g. medicine, biocatalysis and bio-fuels . DNA with errors ( mutations ) is duplicated and the most promising results are incorporated into microbes for the genetic production of the corresponding proteins. She made her first attempts in 1996 to optimize an enzyme ( subtilisin E) that occurs naturally in bacteria for an organic rather than aqueous environment. She holds over 30 US patents (2011) and has advised numerous biotechnology and pharmaceutical companies, such as Merck Sharp & Dohme, on the development of the diabetes drug Januvia .

She developed substances that couple to neurotransmitters and promise improved imaging methods for exploring the brain, where functional magnetic resonance imaging has so far been based primarily on the oxygen content of the blood.

The enzymatic formation of carbon-silicon bonds has also been described by her group. Similarly, a highly selective method of enzymatic representation of was cyclopropane - precursor in the synthesis of ticagrelor described.

In 2005 she co-founded Gevo Inc., which develops methods for producing bio-fuels. She developed an enzyme that works under anaerobic conditions and thus saves high ventilation costs. She works on enzymes that extract biofuel from cellulose instead of sugar.

Personal

She has three sons. In 2005 she developed breast cancer and had an operation. Her hobbies include diving, hiking, cycling and traveling.

honors and awards

Memberships

Fonts

  • with KQ Chen: Enzyme engineering for nonaqueous solvents: random mutagenesis to enhance activity of subtilisin E in polar organic media. Biotechnology (NY), Vol. 9, 1991, pp. 1073-1077.
  • with K. Chen: Tuning the activity of an enzyme for unusual environments: sequential random mutagenesis of subtilisin E for catalysis in dimethylformamide. Proc Natl Acad Sci USA, Vol. 90, 1993, pp. 5618-5622.
  • Engineering proteins for unusual environments. FASEB J., Volume 7, 1993, pp. 744-749.
  • with K. Miyazaki: Exploring nonnatural evolutionary pathways by saturation mutagenesis: rapid improvement of protein function. J. Mol. Evol., Vol. 49, 1996, pp. 716-720.
  • Directed Evolution: Creating Biocatalysts for the Future. In: Chemical Engineering Science. Volume 51, 1996, pp. 5091-5102, doi: 10.1016 / S0009-2509 (96) 00288-6 .
  • with JC Moore, HM Jin, O. Kuchner: Strategies for the in vitro Evolution of Protein Function: Enzyme Evolution by Random Recombination of Improved Sequences. In: Journal of Molecular Biology . Volume 272, 1997, pp. 336-347, pdf .
  • with H. Zhao: Functional and nonfunctional mutations distinguished by random recombination of homologous genes, Proc Natl Acad Sci. USA, Vol. 94, 1997, pp. 7997-8000.
  • with H. Zhao: Optimization of DNA shuffling for high fidelity recombination. Nucleic Acids Res., Vol. 25, 1997, pp. 1307-1308.
  • with H. Zhao, L. Giver, Z. Shao, JA Affholter: Molecular evolution by staggered extension process (StEP) in vitro recombination. Nat Biotechnology, Vol. 16. 1998, pp. 258-261.
  • with L. You: Directed evolution of subtilisin E in Bacillus subtilis to enhance total activity in aqueous dimethylformamide, Protein Eng., Volume 1996, 1994, pp. 77-83.
  • with JC Moore: Directed evolution of a para-nitrobenzyl esterase for aqueous-organic solvents. Nature Biotechnology, Vol. 14, 1996, pp. 458-467.
  • with Z. Shao, H. Zhao, L. Giver: Random-priming in vitro recombination: an effective tool for directed evolution. Nucleic Acids Res., Vol. 26, 1998, pp. 681-683.
  • with L. Giver, A. Gershenson, PO Freskgard: Directed evolution of a thermostable esterase. Proc. Nat. Acad. Sci. USA, Vol. 95, 1998, pp. 12809-12813.
  • Design by Directed Evolution. In: Accounts of Chemical Research . Volume 31, 1998, pp. 125-131, pdf
  • with HM Zhao: Directed evolution coverts subtilisin E into a functional equivalent of thermitase. Protein Eng., Vol. 12, 1999, pp. 47-53.
  • with K. Miyazaki: Exploring non-natural evolutionary pathways by saturation mutagenesis: rapid improvement of protein function. J. Mol. Evol., Vol. 49, 1999, pp. 716-720.
  • with V. Sieber, CA Martinez: Libraries of hybrid proteins from distantly related sequences. Nature Biotechnology, Vol. 19, 2001, pp. 456-460.
  • with CA Voigt, C. Martinez, ZG Wang, SL Mayo: Protein building blocks preserved by recombination. Nature Struct. Biology, Vol. 9, 2002, pp. 553-558.
  • with Phillip A. Romero: Exploring protein fitness landscapes by directed evolution. In: Nature Reviews Molecular Cell Biology . Volume 10, 2009, pp. 866-876, doi: 10.1038 / nrm2805 .
  • The nature of chemical innovation: new enzymes by evolution. The Quarterly Review of Biology, Volume 48, 2015, pp. 404-410.
  • Directed evolution: bringing new chemistry to life. Angew. Chem. Int. Ed., Volume 57, 2018, pp. 4143-4148.

Web links

Commons : Frances Arnold  - collection of images, videos and audio files

Individual evidence

  1. You, Arnold: Directed Evolution of Subtilisin E in Bacillus Subtilis for Catalysis of Dimethylformamide. In: Protein Engineering. Volume 9, 1996, pp. 77-83.
  2. Kan SB, Lewis RD, Chen K, Arnold FH: Directed evolution of cytochrome c for carbon-silicon bond formation: Bringing silicon to life. , Science. 2016 Nov 25; 354 ​​(6315): 1048-1051, PMID 27885032
  3. Hernandez KE, Renata H, Lewis RD, Jennifer Kan SB, Zhang C, Forte J, Rozzell D, McIntosh JA, Arnold FH: Highly Stereoselective Biocatalytic Synthesis of Key Cyclopropane Intermediate to Ticagrelor. , ACS Catal. 2016 Nov 4; 6 (11): 7810-7813, PMID 28286694
  4. ^ MIT Technology Review, 2013 .