Half of the 2018 Nobel Prize in Chemistry was awarded to Professor Frances H. Arnold for her work in the directed evolution of enzymes, while the other half of the prize was split by Professor George P. Smith and Sir Gregory P. Winter for their research into the phage display of peptides and antibodies. Professor […]
Half of the 2018 Nobel Prize in Chemistry was awarded to Professor Frances H. Arnold for her work in the directed evolution of enzymes, while the other half of the prize was split by Professor George P. Smith and Sir Gregory P. Winter for their research into the phage display of peptides and antibodies.
Professor Arnold performed the first directed evolution of enzymes in 1993, using mutation and selection to develop improvements to subtilisin that would be difficult, if not impossible, to discover purely through rational design. She has refined this process since then, developing methods that can be used to discover new catalysts. Her research has implications for a variety of fields, including green chemical manufacturing, renewable fuels, and drug development.
Professor Smith developed a method for using viruses that infect bacteria to evolve new proteins, a process known as phage display. Sir Winter applied this technique to the directed evolution of antibodies. This approach has already led to the discovery of antibodies that can be used to treat rheumatoid arthritis, psoriasis, and inflammatory bowel diseases, as well as neutralize toxins, counteract autoimmune diseases, and cure metastatic cancer.
Professor Arnold is the Linus Pauling Professor of Chemical Engineering, Bioengineering, and Biochemistry at the California Institute of Technology. She is a 32-year member of the American Chemical Society and serves on the Editorial Advisory Board of ACS Central Science. In 2005, ACS honored her with the Francis P. Garvan-John M. Olin Medal, which recognizes distinguished service to chemistry by women chemists. She has published more than 40 articles and book chapters in ACS Publications, as well as on ChemRxiv. Please enjoy the following papers that relate to her prize-winning discoveries. The papers are free to read for 30 days in honor of her achievement:
Synthesis of β-Branched Tryptophan Analogues Using an Engineered Subunit of Tryptophan Synthase
J. Am. Chem. Soc., 2016, 138 (27), pp 8388–8391
DOI: 10.1021/jacs.6b04836
Improved Synthesis of 4-Cyanotryptophan and Other Tryptophan Analogues in Aqueous Solvent Using Variants of TrpB from Thermotoga maritima
J. Org. Chem., 2018, 83 (14), pp 7447–7452
DOI: 10.1021/acs.joc.8b00517
Directed Evolution Mimics Allosteric Activation by Stepwise Tuning of the Conformational Ensemble
J. Am. Chem. Soc., 2018, 140 (23), pp 7256–7266
DOI: 10.1021/jacs.8b03490
Highly Stereoselective Biocatalytic Synthesis of Key Cyclopropane Intermediate to Ticagrelor
ACS Catal., 2016, 6 (11), pp 7810–7813
DOI: 10.1021/acscatal.6b02550
Tryptophan Phosphorescence Study of Enzyme Flexibility and Unfolding in Laboratory-Evolved
Biochemistry, 2000, 39 (16), pp 4658–4665
DOI: 10.1021/bi992473s
Tryptophan Synthase Uses an Atypical Mechanism To Achieve Substrate Specificity
Biochemistry, 2016, 55 (51), pp 7043–7046
DOI: 10.1021/acs.biochem.6b01127
Chemomimetic Biocatalysis: Exploiting the Synthetic Potential of Cofactor-Dependent Enzymes To Create New Catalysts
J. Am. Chem. Soc., 2015, 137 (44), pp 13992–14006
DOI: 10.1021/jacs.5b09348
Professor Smith is the Curators’ Distinguished Professor Emeritus of Biological Sciences at the University of Missouri-Columbia. He has published in ACS journals several times over the years, including this 1997 review of his work on phage display, which is free to read for 30 days in recognition of his achievement.
Phage Display
Chem. Rev., 1997, 97 (2), pp 391–410
DOI: 10.1021/cr960065d
Sir Winter is the Master of Trinity College and Research Leader Emeritus, MRC Laboratory of Molecular Biology, Cambridge. He is the founder of Cambridge Antibody Technology, Domantis, and Bicycle Therapeutics Limited. His publishing relationship with ACS goes back more than 35 years, with articles in Biochemistry and ACS Chemical Biology.