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Polar Substitutions on the Surface of a Lipase Substantially Improve Tolerance in Organic Solvents
Author(s) -
Cui Haiyang,
Vedder Markus,
Zhang Lingling,
Jaeger KarlErich,
Schwaneberg Ulrich,
Davari Mehdi D.
Publication year - 2022
Publication title -
chemsuschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.412
H-Index - 157
eISSN - 1864-564X
pISSN - 1864-5631
DOI - 10.1002/cssc.202102551
Subject(s) - polar , lipase , biocatalysis , solvation , chemistry , molecular dynamics , protein engineering , bacillus subtilis , enzyme , combinatorial chemistry , organic chemistry , catalysis , computational chemistry , reaction mechanism , molecule , biology , genetics , physics , astronomy , bacteria
Biocatalysis in organic solvents (OSs) enables more efficient routes to the synthesis of various valuable chemicals. However, OSs often reduce enzymatic activity, which limits the use of enzymes in OSs. Herein, we report a comprehensive understanding of interactions between surface polar substitutions and DMSO by integrating molecular dynamics (MD) simulations of 45 variants from Bacillus subtilis lipase A (BSLA) and substitution landscape into a “BSLA‐SSM” library. By systematically analyzing 39 structural‐, solvation‐, and interaction energy‐based observables, we discovered that hydration shell maintenance, DMSO reduction, and decreased local flexibility simultaneously govern the stability of polar variants in OS. Moreover, the fingerprints of 1631 polar‐related variants in three OSs demonstrated that substituting aromatic to polar amino acid(s) hold great potential to highly improve OSs resistance. Hence, surface polar engineering is a powerful strategy to generate OS‐tolerant lipases and other enzymes, thereby adapting the catalyst to the desired reaction and process with OSs.