DOI: 10.1126/science.1188934 ISSN:
Biocatalytic Asymmetric Synthesis of Chiral Amines from Ketones Applied to Sitagliptin Manufacture
Christopher K. Savile, Jacob M. Janey, Emily C. Mundorff, Jeffrey C. Moore, Sarena Tam, William R. Jarvis, Jeffrey C. Colbeck, Anke Krebber, Fred J. Fleitz, Jos Brands, Paul N. Devine, Gjalt W. Huisman, Gregory J. Hughes Biocatalytic Boost
Enzymes tend to direct reactions toward specific products much more selectively than synthetic catalysts. Unfortunately, this selectivity has evolved for cellular purposes and may not promote the sorts of reactions chemists are seeking to enhance (see the Perspective by
Lutz
).
Siegel
et al.
(p.
309
) now describe the design of enzymes that catalyze the bimolecular Diels-Alder reaction, a carbon-carbon bond formation reaction that is central to organic synthesis but unknown in natural metabolism. The enzymes display high stereoselectivity and substrate specificity, and an x-ray structure of the most active enzyme confirms that the structure matches the design.
Savile
et al.
(p.
305
, published online 17 June) applied a directed evolution approach to modify an existing transaminase enzyme so that it recognized a complex ketone in place of its smaller native substrate, and could tolerate the high temperature and organic cosolvent necessary to dissolve this ketone. This biocatalytic reaction improved the production efficiency of a drug that treats diabetes.