Higher structure of cereulide, an emetic toxin from Bacillus cereus, and special comparison with valinomycin, an antibiotic from Streptomyces fulvissimus.
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.
Laboratory of Organic Chemistry, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya, 466-8601, Japan.
Arthit
A
Makarasen
Kenji
K
Yoza
Minoru
M
Isobe
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001409:Bacillus cereus / Q000737:chemistry*; D001427:Bacterial Toxins / Q000737:chemistry* / Q000633:toxicity; D018360:Crystallography, X-Ray; D047630:Depsipeptides / Q000737:chemistry* / Q000633:toxicity; D004639:Emetics / Q000633:toxicity; D008670:Metals / Q000737:chemistry; D008968:Molecular Conformation; D011188:Potassium / Q000737:chemistry; D013302:Streptomyces / Q000737:chemistry*; D014634:Valinomycin / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D047630:Depsipeptides; D004639:Emetics; D008670:Metals; C089294:cereulide; D014634:Valinomycin; D011188:Potassium