Less Unfavorable Salt Bridges on the Enzyme Surface Result in More Organic Cosolvent Resistance
dc.bibliographicCitation.firstPage | 11448 | eng |
dc.bibliographicCitation.issue | 20 | eng |
dc.bibliographicCitation.journalTitle | Angewandte Chemie - International Edition | eng |
dc.bibliographicCitation.lastPage | 11456 | eng |
dc.bibliographicCitation.volume | 60 | eng |
dc.contributor.author | Cui, Haiyang | |
dc.contributor.author | Eltoukhy, Lobna | |
dc.contributor.author | Zhang, Lingling | |
dc.contributor.author | Markel, Ulrich | |
dc.contributor.author | Jaeger, Karl-Erich | |
dc.contributor.author | Davari, Mehdi D. | |
dc.contributor.author | Schwaneberg, Ulrich | |
dc.date.accessioned | 2022-01-31T07:51:27Z | |
dc.date.available | 2022-01-31T07:51:27Z | |
dc.date.issued | 2021 | |
dc.description.abstract | Biocatalysis for the synthesis of fine chemicals is highly attractive but usually requires organic (co-)solvents (OSs). However, native enzymes often have low activity and resistance in OSs and at elevated temperatures. Herein, we report a smart salt bridge design strategy for simultaneously improving OS resistance and thermostability of the model enzyme, Bacillus subtilits Lipase A (BSLA). We combined comprehensive experimental studies of 3450 BSLA variants and molecular dynamics simulations of 36 systems. Iterative recombination of four beneficial substitutions yielded superior resistant variants with up to 7.6-fold (D64K/D144K) improved resistance toward three OSs while exhibiting significant thermostability (thermal resistance up to 137-fold, and half-life up to 3.3-fold). Molecular dynamics simulations revealed that locally refined flexibility and strengthened hydration jointly govern the highly increased resistance in OSs and at 50–100 °C. The salt bridge redesign provides protein engineers with a powerful and likely general approach to design OSs- and/or thermal-resistant lipases and other α/β-hydrolases. © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH | eng |
dc.description.version | publishedVersion | eng |
dc.identifier.uri | https://oa.tib.eu/renate/handle/123456789/7953 | |
dc.identifier.uri | https://doi.org/10.34657/6994 | |
dc.language.iso | eng | eng |
dc.publisher | Weinheim : Wiley-VCH | eng |
dc.relation.doi | https://doi.org/10.1002/anie.202101642 | |
dc.relation.essn | 1521-3773 | |
dc.rights.license | CC BY-NC-ND 4.0 Unported | eng |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | eng |
dc.subject.ddc | 540 | eng |
dc.subject.other | bacillus subtilits lipase A (BSLA) | eng |
dc.subject.other | directed evolution | eng |
dc.subject.other | organic solvent resistance | eng |
dc.subject.other | rational design | eng |
dc.subject.other | salt bridge | eng |
dc.title | Less Unfavorable Salt Bridges on the Enzyme Surface Result in More Organic Cosolvent Resistance | eng |
dc.type | Article | eng |
dc.type | Text | eng |
tib.accessRights | openAccess | eng |
wgl.contributor | DWI | eng |
wgl.subject | Chemie | eng |
wgl.type | Zeitschriftenartikel | eng |
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