Concentrates Chemistry news from the week
▸ Highlights Cancer immunotherapy wins medicine Nobel Laser physics traps Nobel Prize in Physics Cassini’s swan song reveals Saturn ring chemistry Phage display yields new black mamba antivenom Manufacturing challenge leads to death in CAR-T trial BASF decides to exit oil business Restrictions lowered for cannabis-derived drug ACS, Elsevier file new suit against ResearchGate
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Protein evolution wins Nobel 3 scientists win chemistry prize for harnessing evolution to develop novel proteins
es released by the bacteria that have the binding protein of interest on their surface. Sequencing the genetic material of the collected phages yields genes for proteins with desired binding affinity. Winter extended phage display to screening for novel antibodies. In 1990, Winter’s team reported the phage dis-
In Arnold’s technique, she introduces random mutations into the gene for a starting enzyme, expresses the variant genes in bacteria, and screens the mutated enzymes produced by the microbes for desired activity. By repeating this process with the best performers, researchers can find proteins with the desired enzymatic properties in terms of activity, binding affinity, or Frances H. Arnold, George P. Smith, and Gregory P. Winter. specificity. play of a folded and fully functional Arnold conducted the first directed evoantibody fragment called a single-chain lution of enzymes in 1993. In that work, she variable fragment. This first demonstraevolved a version of the enzyme subtilisin tion identified selective antibodies that E that was active at high concentrations could bind hen egg-white lysozyme but of the polar organic solvent dimethylfornot human lysozyme or turkey egg-white mamide. Four rounds of mutagenesis and lysozyme. screening resulted in an enzyme that was Directed evolution and phage display 256 times as active as the (see page 9) have both become widely original enzyme. used methods. For example, Provivi, a Smith reported the company founded by Arnold and two of original phage display her coworkers, uses enzymes developed method in 1985. In this through directed evolution to make inlibrary-based method sect pheromones for pest control. And for screening for proresearchers have used phage display to teins that bind a specific identify antibodies with high binding aftarget molecule, the finity for use as pharmaceuticals. gene for each member “This is a fantastic award that recof the library is insertognizes how laboratory evolution, in a ed in the DNA for coat few short decades, has revolutionized protein III of a phage our ability to tailor the properties of virus. The phage infects biomolecules for applications unimagand reproduces in bacined in nature,” says Donald Hilvert, teria. Scientists can then For a look at the research that earned the laureates a an expert in directed evolution at use the target molecule coveted call from Sweden, watch our newest episode of ETH Zurich.—CELIA ARNAUD as bait to enrich phagSpeaking of Chemistry at cenm.ag/2018nobel.
The 2018 Nobel Prize in Chemistry was awarded to Frances H. Arnold of California Institute of Technology for the directed evolution of enzymes and to George P. Smith of the University of Missouri and Gregory P. Winter of the MRC Laboratory of Molecular Biology for the phage display of peptides and antibodies. Arnold will receive half of the approximately $1 million prize; Smith and Winter will split the other half equally. This year’s prize “recognizes the power of harnessing protein evolution to solve a wide range of problems in the molecular sciences,” says David R. Liu of Harvard University, an expert in directed evolution. “My hat’s off to Smith, Winter, and Arnold for their contributions to this multidisciplinary field that beautifully integrates chemistry, molecular biology, and protein science.” Directed evolution is an iterative lab method involving mutation and screening that speeds up the natural selection process through which life on Earth evolved.
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C&EN | CEN.ACS.ORG | OCTOBER 8, 2018
C R E D I T: CA LT EC H , UN I V ERS I T Y O F M IS S O U R I, A N D MRC LA B ORATO RY O F M O L ECU L AR B I O LO GY (H EAD SH OTS); C& E N /ACS P RO DU CT I O N S (SCR E E N S H OT )
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NOBEL PRIZE
