Regioselective Acetylation of C21 Hydroxysteroids by the Bacterial Chloramphenicol Acetyltransferase I |
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Authors: | Azzam Mosa Dr Michael C Hutter Dr Josef Zapp Prof Dr Rita Bernhardt Dr Frank Hannemann |
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Affiliation: | 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) |
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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. |
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Keywords: | acetylation biotransformations chloramphenicol acetyltransferases regioselectivity steroids |
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