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Mechanism-Guided Discovery of an Esterase Scaffold with Promiscuous Amidase Activity
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.ORCID iD: 0000-0002-1685-4735
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.ORCID iD: 0000-0002-4066-2776
2016 (English)In: CATALYSTS, ISSN 2073-4344, Vol. 6, no 6, 90Article in journal (Refereed) Published
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Text
Abstract [en]

The discovery and generation of biocatalysts with extended catalytic versatilities are of immense relevance in both chemistry and biotechnology. An enhanced atomistic understanding of enzyme promiscuity, a mechanism through which living systems acquire novel catalytic functions and specificities by evolution, would thus be of central interest. Using esterase-catalyzed amide bond hydrolysis as a model system, we pursued a simplistic in silico discovery program aiming for the identification of enzymes with an internal backbone hydrogen bond acceptor that could act as a reaction specificity shifter in hydrolytic enzymes. Focusing on stabilization of the rate limiting transition state of nitrogen inversion, our mechanism-guided approach predicted that the acyl hydrolase patatin of the alpha/beta phospholipase fold would display reaction promiscuity. Experimental analysis confirmed previously unknown high amidase over esterase activity displayed by the first described esterase machinery with a protein backbone hydrogen bond acceptor to the reacting NH-group of amides. The present work highlights the importance of a fundamental understanding of enzymatic reactions and its potential for predicting enzyme scaffolds displaying alternative chemistries amenable to further evolution by enzyme engineering.

Place, publisher, year, edition, pages
MDPI AG , 2016. Vol. 6, no 6, 90
Keyword [en]
enzyme promiscuity, enzyme catalysis, biocatalysis, reaction mechanisms, molecular modeling, amidase, esterase
National Category
Engineering and Technology
Identifiers
URN: urn:nbn:se:kth:diva-189936DOI: 10.3390/catal6060090ISI: 000378839100015Scopus ID: 2-s2.0-84975302338OAI: oai:DiVA.org:kth-189936DiVA: diva2:950210
Note

QC 20160728

Available from: 2016-07-28 Created: 2016-07-25 Last updated: 2016-07-28Bibliographically approved

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CiteExportLink to record
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