Recombinant expression and characterization of novel P450s from Actinosynnema mirum

Schmitz LM, Hageneier F, Rosenthal K, Busche T, Brandt D, Kalinowski J, Lutz S (2021)
Bioorganic & medicinal chemistry 42: 116241.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Schmitz, Lisa Marie; Hageneier, Felix; Rosenthal, Katrin; Busche, TobiasUniBi; Brandt, DavidUniBi ; Kalinowski, JörnUniBi; Lutz, Stephan
Abstract / Bemerkung
Cytochrome P450 monooxygenases (P450s) are the major contributor in the metabolism of xenobiotics, including therapeutic agents. Thus, P450s find broad application in the pharmaceutical industry to synthesize metabolites of new active pharmaceutical ingredients in order to evaluate toxicity and pharmacokinetics. As an alternative to human hepatic P450s, microbial P450s offer several advantages, such as an easier and more efficient heterologous expression as well as higher stability under process conditions. Recently, the wild-type strain Actinosynnema mirum has been reported to catalyze hydroxylation reactions with high activity on a broad range of substrates. In this study, one of these substrates, ritonavir, was used to analyze the transcriptional response of the wild-type strain. Analysis of the differential gene expression pattern allowed the assignment of genes potentially responsible for ritonavir conversion. Heterologous expression of these candidates and activity testing led to the identification of a novel P450 that efficiently converts ritonavir resembling the activity of the human CYP3A4. Copyright © 2021. Published by Elsevier Ltd.
Erscheinungsjahr
2021
Zeitschriftentitel
Bioorganic & medicinal chemistry
Band
42
Art.-Nr.
116241
eISSN
1464-3391
Page URI
https://pub.uni-bielefeld.de/record/2955919

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Schmitz LM, Hageneier F, Rosenthal K, et al. Recombinant expression and characterization of novel P450s from Actinosynnema mirum. Bioorganic & medicinal chemistry. 2021;42: 116241.
Schmitz, L. M., Hageneier, F., Rosenthal, K., Busche, T., Brandt, D., Kalinowski, J., & Lutz, S. (2021). Recombinant expression and characterization of novel P450s from Actinosynnema mirum. Bioorganic & medicinal chemistry, 42, 116241. https://doi.org/10.1016/j.bmc.2021.116241
Schmitz, L. M., Hageneier, F., Rosenthal, K., Busche, T., Brandt, D., Kalinowski, J., and Lutz, S. (2021). Recombinant expression and characterization of novel P450s from Actinosynnema mirum. Bioorganic & medicinal chemistry 42:116241.
Schmitz, L.M., et al., 2021. Recombinant expression and characterization of novel P450s from Actinosynnema mirum. Bioorganic & medicinal chemistry, 42: 116241.
L.M. Schmitz, et al., “Recombinant expression and characterization of novel P450s from Actinosynnema mirum”, Bioorganic & medicinal chemistry, vol. 42, 2021, : 116241.
Schmitz, L.M., Hageneier, F., Rosenthal, K., Busche, T., Brandt, D., Kalinowski, J., Lutz, S.: Recombinant expression and characterization of novel P450s from Actinosynnema mirum. Bioorganic & medicinal chemistry. 42, : 116241 (2021).
Schmitz, Lisa Marie, Hageneier, Felix, Rosenthal, Katrin, Busche, Tobias, Brandt, David, Kalinowski, Jörn, and Lutz, Stephan. “Recombinant expression and characterization of novel P450s from Actinosynnema mirum”. Bioorganic & medicinal chemistry 42 (2021): 116241.

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