Regioselective Acetylation of C21 Hydroxysteroids by the Bacterial Chloramphenicol Acetyltransferase I

  • Chembiochem. 2015 Jul 27;16(11):1670-9. doi: 10.1002/cbic.201500125.
Azzam Mosa  1 ,  Michael C Hutter  2 ,  Josef Zapp  3 ,  Rita Bernhardt  1 ,  Frank Hannemann  4
Affiliations
  • 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). [email protected].
PMID: 25999128 DOI: 10.1002/cbic.201500125
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.
Products