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Higher Structure of Cereulide, an Emetic Toxin from Bacillus cereus , and Special Comparison with Valinomycin, an Antibiotic from Streptomyces fulvissimus
Author(s) -
Makarasen Arthit,
Yoza Kenji,
Isobe Minoru
Publication year - 2009
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.200900011
Subject(s) - valinomycin , bacillus cereus , ionophore , chemistry , stereochemistry , cereus , crystallography , biochemistry , membrane potential , bacteria , biology , membrane , genetics
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 1 H 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.