Format

Send to

Choose Destination
Angew Chem Int Ed Engl. 2018 Mar 5;57(11):2864-2868. doi: 10.1002/anie.201713189. Epub 2018 Feb 15.

Kinetic Resolution of sec-Thiols by Enantioselective Oxidation with Rationally Engineered 5-(Hydroxymethyl)furfural Oxidase.

Author information

1
Department of Chemistry, University of Graz, Heinrichstrasse 28, 8010, Graz, Austria.
2
Department of Biotechnology, University of Groningen, Nijenborgh 4, 9747AG, Groningen, The Netherlands.
3
Austrian Centre of Industrial Biotechnology (ACIB GmbH), c/o Heinrichstrasse 28, 8010, Graz, Austria.
4
Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Via Ferrata 9, 27100, Pavia, Italy.

Abstract

Various flavoprotein oxidases were recently shown to oxidize primary thiols. Herein, this reactivity is extended to sec-thiols by using structure-guided engineering of 5-(hydroxymethyl)furfural oxidase (HMFO). The variants obtained were employed for the oxidative kinetic resolution of racemic sec-thiols, thus yielding the corresponding thioketones and nonreacted R-configured thiols with excellent enantioselectivities (E≥200). The engineering strategy applied went beyond the classic approach of replacing bulky amino acid residues with smaller ones, as the active site was additionally enlarged by a newly introduced Thr residue. This residue established a hydrogen-bonding interaction with the substrates, as verified in the crystal structure of the variant. These strategies unlocked HMFO variants for the enantioselective oxidation of a range of sec-thiols.

KEYWORDS:

biocatalysis; enzymes; kinetic resolution; oxidation; thiols

PMID:
29384246
DOI:
10.1002/anie.201713189
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center