Biosynthesis of the beta-Lactone Proteasome Inhibitors Belactosin and Cystargolide

Wolf F, Bauer JS, Bendel TM, Kulik A, Kalinowski J, Gross H, Kaysser L (2017)
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 56(23): 6665-6668.

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Belactosins and cystargolides are natural product proteasome inhibitors from Actinobacteria. Both feature dipeptidic backbones and a unique beta-lactone building block. Herein, we present a detailed investigation of their biosynthesis. Identification and analysis of the corresponding gene clusters indicated that both compounds are assembled by rare single-enzyme amino acid ligases. Feeding experiments with isotope-labeled precursors and in vitro biochemistry showed that the formation of the beta-lactone warhead is unprecedented and reminiscent of leucine biosynthesis, and that it involves the action of isopropylmalate synthase homologues.
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Wolf F, Bauer JS, Bendel TM, et al. Biosynthesis of the beta-Lactone Proteasome Inhibitors Belactosin and Cystargolide. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION. 2017;56(23):6665-6668.
Wolf, F., Bauer, J. S., Bendel, T. M., Kulik, A., Kalinowski, J., Gross, H., & Kaysser, L. (2017). Biosynthesis of the beta-Lactone Proteasome Inhibitors Belactosin and Cystargolide. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 56(23), 6665-6668. doi:10.1002/anie.201612076
Wolf, F., Bauer, J. S., Bendel, T. M., Kulik, A., Kalinowski, J., Gross, H., and Kaysser, L. (2017). Biosynthesis of the beta-Lactone Proteasome Inhibitors Belactosin and Cystargolide. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 56, 6665-6668.
Wolf, F., et al., 2017. Biosynthesis of the beta-Lactone Proteasome Inhibitors Belactosin and Cystargolide. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 56(23), p 6665-6668.
F. Wolf, et al., “Biosynthesis of the beta-Lactone Proteasome Inhibitors Belactosin and Cystargolide”, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, vol. 56, 2017, pp. 6665-6668.
Wolf, F., Bauer, J.S., Bendel, T.M., Kulik, A., Kalinowski, J., Gross, H., Kaysser, L.: Biosynthesis of the beta-Lactone Proteasome Inhibitors Belactosin and Cystargolide. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION. 56, 6665-6668 (2017).
Wolf, Felix, Bauer, Judith S., Bendel, Theresa M., Kulik, Andreas, Kalinowski, Jörn, Gross, Harald, and Kaysser, Leonard. “Biosynthesis of the beta-Lactone Proteasome Inhibitors Belactosin and Cystargolide”. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 56.23 (2017): 6665-6668.
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