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Synfacts 2011(3): 0323-0323  
DOI: 10.1055/s-0030-1259455
Organo- and Biocatalysis
© Georg Thieme Verlag Stuttgart ˙ New York

A Biocatalytic Diels-Alder Reaction Using a Designed Enzyme

Contributor(s): Benjamin List, Olga Lifchits
J. B. Siegel, A. Zanghellini, H. M. Lovick, G. Kiss, A. R. Lambert, J. L. St.Clair, J. L. Gallaher, D. Hilvert, M. H. Gelb, B. L. Stoddard, K. N. Houk, F. E. Michael, D. Baker*
ETH Zürich, Switzerland; University of Washington, University of California, Los Angeles and Fred Hutchinson Cancer Research Center, Seattle, USA
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Publication History

Publication Date:
16 February 2011 (online)

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Significance

David Baker and collaborators from the fields of biochemistry, computational chemistry and synthetic organic chemistry have successfully developed enzymes that can catalyze a bimolecular Diels-Alder reaction, a process essentially unknown with naturally occurring enzymes. Using computational methods, the team designed an active site, which catalyzes the reaction by modulating the molecular orbital energies (HOMO and LUMO) of the two reactive partners 1 and 2 as well as positioning them in a proper orientation. Biochemical synthesis followed by active site optimization identified two enzymes, which display ­extremely high specificity and stereoselectivity (er > 98.5:1.5, dr > 99:1) in a model Diels-Alder reaction.