Characterization of the Actinonin Biosynthetic Gene Cluster

Wolf F, Leipoldt F, Kulik A, Wibberg D, Kalinowski J, Kaysser L (2018)
CHEMBIOCHEM 19(11): 1189-1195.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Abstract / Bemerkung
The hydroxamate moiety of the natural product actinonin mediates inhibition of metalloproteinases because of its chelating properties towards divalent cations in the active site of those enzymes. Owing to its antimicrobial activity, actinonin has served as a lead compound for the development of new antibiotic drug candidates. Recently, we identified a putative gene cluster for the biosynthesis of actinonin. Here, we confirm and characterize this cluster by heterologous pathway expression and gene-deletion experiments. We assigned the biosynthetic gene cluster to actinonin production and determine the cluster boundaries. Furthermore, we establish that ActI, an AurF-like oxygenase, is responsible for the N-hydroxylation reaction that forms the hydroxamate warhead. Our findings provide the basis for more detailed investigations of actinonin biosynthesis.
Stichworte
biosynthesis; heterologous expression; inhibitors; metabolism; natural; products
Erscheinungsjahr
2018
Zeitschriftentitel
CHEMBIOCHEM
Band
19
Ausgabe
11
Seite(n)
1189-1195
ISSN
1439-4227
eISSN
1439-7633
Page URI
https://pub.uni-bielefeld.de/record/2921235

Zitieren

Wolf F, Leipoldt F, Kulik A, Wibberg D, Kalinowski J, Kaysser L. Characterization of the Actinonin Biosynthetic Gene Cluster. CHEMBIOCHEM. 2018;19(11):1189-1195.
Wolf, F., Leipoldt, F., Kulik, A., Wibberg, D., Kalinowski, J., & Kaysser, L. (2018). Characterization of the Actinonin Biosynthetic Gene Cluster. CHEMBIOCHEM, 19(11), 1189-1195. doi:10.1002/cbic.201800116
Wolf, F., Leipoldt, F., Kulik, A., Wibberg, D., Kalinowski, J., and Kaysser, L. (2018). Characterization of the Actinonin Biosynthetic Gene Cluster. CHEMBIOCHEM 19, 1189-1195.
Wolf, F., et al., 2018. Characterization of the Actinonin Biosynthetic Gene Cluster. CHEMBIOCHEM, 19(11), p 1189-1195.
F. Wolf, et al., “Characterization of the Actinonin Biosynthetic Gene Cluster”, CHEMBIOCHEM, vol. 19, 2018, pp. 1189-1195.
Wolf, F., Leipoldt, F., Kulik, A., Wibberg, D., Kalinowski, J., Kaysser, L.: Characterization of the Actinonin Biosynthetic Gene Cluster. CHEMBIOCHEM. 19, 1189-1195 (2018).
Wolf, Felix, Leipoldt, Franziska, Kulik, Andreas, Wibberg, Daniel, Kalinowski, Jörn, and Kaysser, Leonard. “Characterization of the Actinonin Biosynthetic Gene Cluster”. CHEMBIOCHEM 19.11 (2018): 1189-1195.

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