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)