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Expanding the enzyme universe through a marriage of chemistry and evolution

Arnold, Frances H. (2013) Expanding the enzyme universe through a marriage of chemistry and evolution. In: New chemistry and new opportunities from the expanding protein universe. World Scientific , Hackensack, NJ, pp. 84-89. ISBN 978-981-4603-82-9.

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For more than twenty years this laboratory has used directed evolution to modify enzymes. It is now widely accepted that directed evolution can change substrate specificity or reaction selectivity in desired ways, even if it sometimes remains difficult in practice. It is no longer surprising that enzymes adapt readily by accumulating beneficial mutations. And why should it be, since this is how Nature tailors them for myriad biological roles? More difficult to grasp is how Nature discovers new enzyme functions, particularly new catalytic activities. We know that the biological world's diverse catalytic repertoire is the product of evolution by natural selection, but we have little understanding of how Nature's tinkering generates new functions. Sometimes we are (un)lucky enough to catch them in the act - e.g., the acquisition of antibiotic resistance or the ability to degrade man-made toxins. But for the vast majority of activities, the fossil record is nonexistent or too sparse to tell the molecular story. This leaves us without much guidance for evolving new enzymes in the laboratory. Consequently we are forced to contaminate our evolution experiments with knowledge - e.g., computational design [1, 2] - in order to jumpstart the discovery process.

Item Type:Book Section
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Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2014 World Scientific. I have described the work of highly talented graduate students and postdocs: Pedro Coelho, Eric Brustad, John Mcintosh, Jane Wang and Chris Farwell. Support was received from the Jacobs Institute for Molecular Engineering for Medicine at Caltech, and the Gordon and Betty Moore Foundation through Grant GBMF2809 to the Caltech Programmable Molecular Technology Initiative.
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Jacobs Institute for Molecular Engineering for MedicineUNSPECIFIED
Gordon and Betty Moore FoundationGBMF2809
Record Number:CaltechAUTHORS:20150519-132607405
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:57664
Deposited By: Tony Diaz
Deposited On:19 May 2015 20:49
Last Modified:10 Nov 2021 21:53

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