Higher Structure of Cereulide, an Emetic Toxin from Bacillus cereus, and Special Comparison with Valinomycin, an Antibiotic from Streptomyces fulvissimus
Article first published online: 3 APR 2009
Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chemistry – An Asian Journal
Volume 4, Issue 5, pages 688–698, May 4, 2009
How to Cite
Makarasen, A., Yoza, K. and Isobe, M. (2009), Higher Structure of Cereulide, an Emetic Toxin from Bacillus cereus, and Special Comparison with Valinomycin, an Antibiotic from Streptomyces fulvissimus. Chem. Asian J., 4: 688–698. doi: 10.1002/asia.200900011
- Issue published online: 28 APR 2009
- Article first published online: 3 APR 2009
- Manuscript Received: 8 JAN 2009
- natural products;
- X-ray absorption spectroscopy
Not to be confused: Cereulide is an emetic toxin produced by Bacillus cereus through an unusual non-ribosomal peptide synthesis, whereas valinomycin, produced by Streptomyces fulvissimus, is a known antibiotic drug. Cereulide has a greater complexation ability with metal ions than valinomycin and also exhibits a K+-ion-selective ionophore property at lower concentrations than valinomycin.
Cereulide and valinomycin are both 36-membered cyclic depsipeptides with 12 stereogenic centers that have a very similar sequence of cyclo [-D-O-Leu-D-Ala-L-O-Val-L-Val-]3 and cyclo [-D-O-Val-D-Val-L-O-Ala-L-Val-]3, respectively. Cereulide is an emetic toxin produced by Bacillus cereus through an unusual non-ribosomal peptide synthesis (NRPS), whereas valinomycin, produced by Streptomyces fulvissimus, is a known antibiotic drug. Both compounds are known as K+-ion-selective ionophores and cause a potassium-dependent drop in the transmembrane potential of mitochondria, arising from the uptake of a K+-ion-charged ionophore complex. Such compounds may affect mitochondrial function. In the three-dimensional structure of cereulide and valinomycin, cereulide has a vertical and horizontal mirror-image-like structure as is the case in valinomycin. The only difference is the side chains which are linked to a similar framework. Through the current 1H NMR spectroscopy and metal-complexation studies, we found that cereulide had a higher complexation ability to metal ions compared to valinomycin. Cereulide exhibited the K+-ion-selective ionophore property at a lower concentration than valinomycin. X-ray crystallographic analyses of the cereulide and valinomycin H+ form were compared, and revealed that the higher structures of both compounds also showed similarity in the crystal structures. The structure of cereulide–H+ form was found to be in agreement with the structure obtained by a combination of NMR spectroscopy and molecular-mechanics calculations, which afforded reasonable dihedral angles at the local-minimum-energy conformation of the cereulide–K+-ion complex.