Baceridin, a cyclic hexapeptide from an epiphytic bacillus strain, inhibits the proteasome
- authored by
- Jutta Niggemann, Przemyslaw Bozko, Nicole Bruns, Anne Wodtke, Marc Timo Gieseler, Kevin Thomas, Christine Jahns, Manfred Nimtz, Inge Reupke, Thomas Brüser, Georg Auling, Nisar Malek, Markus Kalesse
- Abstract
A new cyclic hexapeptide, baceridin (1), was isolated from the culture medium of a plant-associated Bacillus strain. The structure of 1 was elucidated by HR-HPLC-MS and 1D and 2D NMR experiments and confirmed by ESI MS/MS sequence analysis of the corresponding linear hexapeptide 2. The absolute configurations of the amino acid residues were determined after derivatization by GC-MS and Marfey's method. The cyclopeptide 1 consists partially of nonribosomal-derived D- and allo-D-configured amino acids. The order of the D- and L-leucine residues within the sequence cyclo(-L-Trp-D-Ala-D-allo-Ile-L-Val-D-Leu-L-Leu-) was assigned by total synthesis of the two possible stereoisomers. Baceridin (1) was tested for antimicrobial and cytotoxic activity and displayed moderate cytotoxicity (1-2 μg-‰mL-1) as well as weak activity against Staphylococcus aureus. However, it was identified to be a proteasome inhibitor that inhibits cell cycle progression and induces apoptosis in tumor cells by a p53-independent pathway. Go your own way: The cyclic hexapeptide baceridin was isolated from the culture medium of a plant-associated Bacillus strain. The configuration could be assigned by chemical degradation and total synthesis. In the course of biological validations baceridin was identified as a proteasome inhibitor that inhibits cell-cycle progression and induces apoptosis in tumor cells by a p53-independent pathway.
- Organisation(s)
-
Institute of Microbiology
Institute of Organic Chemistry
- External Organisation(s)
-
Helmholtz Centre for Infection Research (HZI)
University of Tübingen
- Type
- Article
- Journal
- CHEMBIOCHEM
- Volume
- 15
- Pages
- 1021-1029
- No. of pages
- 9
- ISSN
- 1439-4227
- Publication date
- 05.05.2014
- Publication status
- Published
- Peer reviewed
- Yes
- ASJC Scopus subject areas
- Biochemistry, Molecular Medicine, Molecular Biology, Organic Chemistry
- Electronic version(s)
-
https://doi.org/10.1002/cbic.201300778 (Access:
Closed)