Higher Structure of Cereulide, an Emetic Toxin from Bacillus cereus, and Special Comparison with Valinomycin, an Antibiotic from Streptomyces fulvissimus

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. magnified image 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.