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Issue 48, 2017
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Addition of a polyhistidine tag alters the regioselectivity of carbonyl reductase S1 from Candida magnoliae

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Abstract

Studying enzymatic reductions of substrates with more than a single keto group is challenging, as the carbonyl reduction can create a vast array of regio- and stereoisomers. If used as reference compounds, regio- and stereopure hydroxy ketides could facilitate the characterization of reductases with unclear regio- and stereoselectivity. We have combined nonenzymatic and enzymatic reduction and oxidation steps to obtain all four regio- and stereoisomers of tert-butyl hydroxyoxohexanoates in high optical purity (enantiomeric ratio (er) of 99 : 1 for the δ-hydroxy-β-keto isomers; er of >97 : 3 for the β-hydroxy-δ-keto isomers). Furthermore, we have prepared seven of the eight possible regioisomers and diastereomers of γ-methylated hydroxyoxohexanoates. These 11 compounds allowed unraveling the complex stereoselectivity of β,δ-diketo ester reductions catalyzed by carbonyl reductase S1 from Candida magnoliae (CMCR-S1). Our analysis shows that the regio- and stereoselectivity of CMCR-S1-catalyzed reductions is highly sensitive toward modifications at the C-terminus of CMCR-S1: in addition to the expected δ-hydroxy product, the variant with a C-terminal His-tag also led to formation of β-hydroxy by-products with high optical purity.

Graphical abstract: Addition of a polyhistidine tag alters the regioselectivity of carbonyl reductase S1 from Candida magnoliae

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Publication details

The article was received on 30 Oct 2017, accepted on 23 Nov 2017 and first published on 23 Nov 2017


Article type: Paper
DOI: 10.1039/C7OB02666H
Citation: Org. Biomol. Chem., 2017,15, 10256-10264
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    Addition of a polyhistidine tag alters the regioselectivity of carbonyl reductase S1 from Candida magnoliae

    J. Haas, M. Häckh, V. Justus, M. Müller and S. Lüdeke, Org. Biomol. Chem., 2017, 15, 10256
    DOI: 10.1039/C7OB02666H

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