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Chembiochem. 2015 Jul 27;16(11):1670-9. doi: 10.1002/cbic.201500125. Epub 2015 Jun 12.

Regioselective Acetylation of C21 Hydroxysteroids by the Bacterial Chloramphenicol Acetyltransferase I.

Author information

1
Institute of Biochemistry, Saarland University, Campus B2.2, 66123 Saarbrücken (Germany).
2
Center for Bioinformatics, Saarland University, Campus E2.1, 66123 Saarbrücken (Germany).
3
Institute of Pharmaceutical Biology, Saarland University, Campus C2.2, 66123 Saarbrücken (Germany).
4
Institute of Biochemistry, Saarland University, Campus B2.2, 66123 Saarbrücken (Germany). f.hannemann@mx.uni-saarland.de.

Abstract

Chloramphenicol acetyltransferase I (CATI) detoxifies the antibiotic chloramphenicol and confers a corresponding resistance to bacteria. In this study we identified this enzyme as a steroid acetyltransferase and designed a new and efficient Escherichia-coli-based biocatalyst for the regioselective acetylation of C21 hydroxy groups in steroids of pharmaceutical interest. The cells carried a recombinant catI gene controlled by a constitutive promoter. The capacity of the whole-cell system to modify different hydroxysteroids was investigated, and NMR spectroscopy revealed that all substrates were selectively transformed into the corresponding 21-acetoxy derivatives. The biotransformation was optimized, and the reaction mechanism is discussed on the basis of a computationally modeled substrate docking into the crystal structure of CATI.

KEYWORDS:

acetylation; biotransformations; chloramphenicol acetyltransferases; regioselectivity; steroids

PMID:
25999128
DOI:
10.1002/cbic.201500125
[Indexed for MEDLINE]

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