Baceridin, a cyclic hexapeptide from an epiphytic bacillus strain, inhibits the proteasome

verfasst von
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.

Organisationseinheit(en)
Institut für Mikrobiologie
Institut für Organische Chemie
Externe Organisation(en)
Helmholtz-Zentrum für Infektionsforschung GmbH (HZI)
Eberhard Karls Universität Tübingen
Typ
Artikel
Journal
CHEMBIOCHEM
Band
15
Seiten
1021-1029
Anzahl der Seiten
9
ISSN
1439-4227
Publikationsdatum
05.05.2014
Publikationsstatus
Veröffentlicht
Peer-reviewed
Ja
ASJC Scopus Sachgebiete
Biochemie, Molekularmedizin, Molekularbiologie, Organische Chemie
Elektronische Version(en)
https://doi.org/10.1002/cbic.201300778 (Zugang: Geschlossen)