How to engineer organic solvent resistant enzymes: Insights from combined molecular dynamics and directed evolution study

05/05/2020
  A molecular dynamics simulation: Bacillus subtilis lipase A surface representation in three organic solvents Copyright: © ChemCatChem Surface charge engineering (introduction of positively charged substitutions) and substrate binding cleft non-polar engineering strategies could serve as general rational principles to stabilize lipases and other enzymes in OSs.

Congratulations Haiyang Cui on his recent Publication!

Expanding synthetic capabilities to routinely employ enzymes in organic solvents is a dream for protein engineers and synthetic chemists. Despite significant advances in the field of protein engineering, general and transferable design principles to improve the organic solvent resistance of enzymes are poorly understood. In Haiyang’s (Ocean) new publication, we report a combined molecular dynamics simulations and directed evolution study of Bacillus subtilis lipase A in three organic solvents ( 1,4-dioxane, dimethyl sulfoxide, 2,2,2-trifluoroethanol) to devise two rational strategies to guide engineering of resistant enzymes (i) surface charge engineering, and (ii) substrate binding cleft engineering. These strategies would assist experimentalists to design organic solvent resistant enzymes with reduced time and screening effort in lab experiments.

This work was realized in the division Computational Biology and was supported by computing resources granted by JARA-HPC from RWTH Aachen University (JARA0169). Haiyang Cui is financially supported by the China Scholarship Council (CSC) scholarship.

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Cui, H., Stadtmüller, T. H., Jiang, Q., Jaeger, K., Schwaneberg, U. and D. Davari, M. (2020), How to engineer organic solvent resistant enzymes: Insights from combined molecular dynamics and directed evolution study. ChemCatChem. Accepted Author Manuscript. doi:10.1002/cctc.202000422