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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 309-313 |
| Number of pages | 5 |
| Journal | Science |
| Volume | 329 |
| Issue number | 5989 |
| DOIs | |
| State | Published - Jul 16 2010 |
| Externally published | Yes |
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ASJC Scopus subject areas
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Cite this
Computational design of an enzyme catalyst for a stereoselective bimolecular diels-alder reaction. / Siegel, Justin; Zanghellini, Alexandre; Lovick, Helena M.; Kiss, Gert; Lambert, Abigail R.; St.Clair, Jennifer L.; Gallaher, Jasmine L.; Hilvert, Donald; Gelb, Michael H.; Stoddard, Barry L.; Houk, Kendall N.; Michael, Forrest E.; Baker, David.
In: Science, Vol. 329, No. 5989, 16.07.2010, p. 309-313.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Computational design of an enzyme catalyst for a stereoselective bimolecular diels-alder reaction
AU - Siegel, Justin
AU - Zanghellini, Alexandre
AU - Lovick, Helena M.
AU - Kiss, Gert
AU - Lambert, Abigail R.
AU - St.Clair, Jennifer L.
AU - Gallaher, Jasmine L.
AU - Hilvert, Donald
AU - Gelb, Michael H.
AU - Stoddard, Barry L.
AU - Houk, Kendall N.
AU - Michael, Forrest E.
AU - Baker, David
PY - 2010/7/16
Y1 - 2010/7/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77954811495&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954811495&partnerID=8YFLogxK
U2 - 10.1126/science.1190239
DO - 10.1126/science.1190239
M3 - Article
VL - 329
SP - 309
EP - 313
JO - Science
JF - Science
SN - 0036-8075
IS - 5989
ER -