Computational design of an enzyme catalyst for a stereoselective bimolecular Diels-Alder reaction.

Science
Justin B SiegelDavid Baker

Abstract

The Diels-Alder reaction is a cornerstone in organic synthesis, forming two carbon-carbon bonds and up to four new stereogenic centers in one step. No naturally occurring enzymes have been shown to catalyze bimolecular Diels-Alder reactions. We describe the de novo computational design and experimental characterization of enzymes catalyzing a bimolecular Diels-Alder reaction with high stereoselectivity and substrate specificity. X-ray crystallography confirms that the structure matches the design for the most active of the enzymes, and binding site substitutions reprogram the substrate specificity. Designed stereoselective catalysts for carbon-carbon bond-forming reactions should be broadly useful in synthetic chemistry.

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Citations

Nov 30, 2012·Journal of Molecular Modeling·Xiaoqiang HuangYushan Zhu
Jun 28, 2012·Molecules and Cells·Seong Eon Ryu, Wayne A Hendrickson
Dec 21, 2011·Journal of Computer-aided Molecular Design·David W Borhani, David E Shaw
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Jun 5, 2012·Journal of the American Chemical Society·Alireza ShokriSteven R Kass
Aug 9, 2012·Journal of the American Chemical Society·Florian RichterDavid Baker
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Aug 13, 2013·Journal of the American Chemical Society·Manfred T Reetz
Aug 9, 2013·Journal of the American Chemical Society·Antony J BurtonDerek N Woolfson
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Jan 12, 2012·ACS Nano·Christopher R SoMehmet Sarikaya
Dec 14, 2012·Nature·Jay D KeaslingPhil S Baran
Nov 9, 2012·Nature·Nobuyasu KogaDavid Baker
Jan 24, 2012·Nature Biotechnology·Christopher B EibenDavid Baker
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Jul 30, 2011·Nature Methods·Monya Baker
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