PROTEIN DESIGN

Designed to stand the heat

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Science  01 Dec 2017:
Vol. 358, Issue 6367, pp. 1144-1145
DOI: 10.1126/science.358.6367.1144-d

Enzymes are valued as catalysts in the synthesis of pharmaceuticals, fine chemicals, and biofuels. A limitation is that most enzymes are unstable under the reaction conditions used in chemical manufacturing. Moore et al. describe a strategy for stabilization based on designing covalent protein staples into an enzyme scaffold. They used Rosetta design software to identify optimal sites for introducing thioether bonds between a cysteine residue and a noncanonical amino acid. The design was implemented in an enzyme used in the biosynthesis of drugs containing cyclopropane. Several rounds of optimization yielded an enzyme containing two staples with enhanced thermal stability and resistance to chemical denaturation and organic solvents. The modified enzyme showed no reduction in activity or selectivity relative to the parent enzyme.

Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1708907114 (2017).

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