Enzyme stabilization via computationally guided protein stapling.

ABSTRACT: Thermostabilization represents a critical and often obligatory step toward enhancing the robustness of enzymes for organic synthesis and other applications. While directed evolution methods have provided valuable tools for this purpose, these protocols are laborious and time-consuming and typically require the accumulation of several mutations, potentially at the expense of catalytic function. Here, we report a minimally invasive strategy for enzyme stabilization that relies on the installation of genetically encoded, nonreducible covalent staples in a target protein scaffold using computational design. This methodology enables the rapid development of myoglobin-based cyclopropanation biocatalysts featuring dramatically enhanced thermostability (ΔT_m = +18.0 °C and ΔT</

SUBMITTER: Moore EJ 

PROVIDER: S-EPMC5703291 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature