Less Unfavorable Salt Bridges on the Enzyme Surface Result in More Organic Cosolvent Resistance

dc.bibliographicCitation.firstPage11448eng
dc.bibliographicCitation.issue20eng
dc.bibliographicCitation.journalTitleAngewandte Chemie - International Editioneng
dc.bibliographicCitation.lastPage11456eng
dc.bibliographicCitation.volume60eng
dc.contributor.authorCui, Haiyang
dc.contributor.authorEltoukhy, Lobna
dc.contributor.authorZhang, Lingling
dc.contributor.authorMarkel, Ulrich
dc.contributor.authorJaeger, Karl-Erich
dc.contributor.authorDavari, Mehdi D.
dc.contributor.authorSchwaneberg, Ulrich
dc.date.accessioned2022-01-31T07:51:27Z
dc.date.available2022-01-31T07:51:27Z
dc.date.issued2021
dc.description.abstractBiocatalysis 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 GmbHeng
dc.description.versionpublishedVersioneng
dc.identifier.urihttps://oa.tib.eu/renate/handle/123456789/7953
dc.identifier.urihttps://doi.org/10.34657/6994
dc.language.isoengeng
dc.publisherWeinheim : Wiley-VCHeng
dc.relation.doihttps://doi.org/10.1002/anie.202101642
dc.relation.essn1521-3773
dc.rights.licenseCC BY-NC-ND 4.0 Unportedeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/eng
dc.subject.ddc540eng
dc.subject.otherbacillus subtilits lipase A (BSLA)eng
dc.subject.otherdirected evolutioneng
dc.subject.otherorganic solvent resistanceeng
dc.subject.otherrational designeng
dc.subject.othersalt bridgeeng
dc.titleLess Unfavorable Salt Bridges on the Enzyme Surface Result in More Organic Cosolvent Resistanceeng
dc.typeArticleeng
dc.typeTexteng
tib.accessRightsopenAccesseng
wgl.contributorDWIeng
wgl.subjectChemieeng
wgl.typeZeitschriftenartikeleng
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