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

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.

SUBMITTER: Siegel JB

PROVIDER: S-EPMC3241958 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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

Siegel Justin B JB Zanghellini Alexandre A Lovick Helena M HM Kiss Gert G Lambert Abigail R AR St Clair Jennifer L JL Gallaher Jasmine L JL Hilvert Donald D Gelb Michael H MH Stoddard Barry L BL Houk Kendall N KN Michael Forrest E FE Baker David D

Science (New York, N.Y.) 20100701 5989

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 desig ...[more]

PMID: 20647463

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