Next Article in Journal
Rh(III)-Catalyzed, Highly Selectively Direct C–H Alkylation of Indoles with Diazo Compounds
Next Article in Special Issue
Controlling Active Site Loop Dynamics in the (β/α)8 Barrel Enzyme Indole-3-Glycerol Phosphate Synthase
Previous Article in Journal
Synthesis of Anchored Bimetallic Catalysts via Epitaxy
Previous Article in Special Issue
Investigation of Structural Dynamics of Enzymes and Protonation States of Substrates Using Computational Tools
Article Menu

Export Article

Open AccessCommunication

Mechanism-Guided Discovery of an Esterase Scaffold with Promiscuous Amidase Activity

Science for Life Laboratory, School of Biotechnology, Division of Proteomics and Nanobiotechnology, KTH Royal Institute of Technology, 171 21 Stockholm, Sweden
School of Chemical Science and Engineering, Division of Applied Physical Chemistry, KTH Royal Institute of Technology, 100 44 Stockholm, Sweden
Author to whom correspondence should be addressed.
Dedicated to Romas Kazlauskas on the occasion of his 60th birthday.
Academic Editors: David D. Boehr and Keith Hohn
Catalysts 2016, 6(6), 90;
Received: 29 March 2016 / Revised: 23 May 2016 / Accepted: 9 June 2016 / Published: 18 June 2016
(This article belongs to the Special Issue Enzyme Catalysis)
PDF [1529 KB, uploaded 18 June 2016]


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 α/β 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. View Full-Text
Keywords: enzyme promiscuity; enzyme catalysis; biocatalysis; reaction mechanisms; molecular modeling; amidase; esterase enzyme promiscuity; enzyme catalysis; biocatalysis; reaction mechanisms; molecular modeling; amidase; esterase

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Kürten, C.; Carlberg, B.; Syrén, P.-O. Mechanism-Guided Discovery of an Esterase Scaffold with Promiscuous Amidase Activity. Catalysts 2016, 6, 90.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Catalysts EISSN 2073-4344 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top