This research was supported by DSM, the FFG, the province of Styria, the SFG, and the city of Graz. We thank H. Mandl from the Research Centre Applied Biocatalysis, I. Wirth and O. Maurer from DSM for excellent technical support, and K. Faber, C. Kratky, and W. Kroutil for valuable comments on the manuscript, and P. Naggl for the color artwork.
Carving the Active Site of Almond R-HNL for Increased Enantioselectivity†
Article first published online: 6 JUL 2005
Copyright © 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 44, Issue 30, pages 4700–4704, July 25, 2005
How to Cite
Weis, R., Gaisberger, R., Skranc, W., Gruber, K. and Glieder, A. (2005), Carving the Active Site of Almond R-HNL for Increased Enantioselectivity. Angew. Chem. Int. Ed., 44: 4700–4704. doi: 10.1002/anie.200500435
- Issue published online: 18 JUL 2005
- Article first published online: 6 JUL 2005
- Manuscript Received: 4 FEB 2005
- ACE inhibitors;
- asymmetric synthesis;
- hydroxynitrile lyase;
- protein engineering
Structure-guided redesign of the active site of almond (R)-PaHNL5 for increased enantioselectivity resulted in four improved muteins. In particular, mutation V360I gave enhanced conversion rates and enantioselectivities higher than 96 % ee for two structurally related substrates 1 and 2. Chiral building blocks for the synthesis of pharmaceutically active “prils” (example shown) can thus be produced on a large scale.