1986 年 106 巻 9 号 p. 729-757
After structure elucidation of 16-membered macrolide antibiotic leucomycin, the structures of spiramycin, tylosin, megalomicin, irumamycin and virustomycin were determined by chemical degradation and nuclear magnetic resonance (NMR) spectroscopy. The studies on the chemical modification and structure activity correlation of macrolides led to the elaboration of clinically useful new derivatives.
The biosynthetic origin of the carbon skeletone of macrolide aglycone was investigated by means of 13C NMR and the feeding experiments of 13C labeled precursors. We found that an antifungal antibiotic cerulenin is a specific inhibitor of fatty acid and “polyketide” biosyntheses, and applied the antibiotic to the biosynthetic studies of macrolides after formation of the lactone ring and to the production of a new “hybrid” macrolide, chimeramycin. Furthermore, a strain which produces a new “hybrid” antibiotic mederrhodin was breaded from actinorhodin and medermycin producers by gene manipulation.
Sixty five or more new antibiotics have been discovered from secondary microbial metabolites using newly devised screening systems. Azureomycins and izupeptins were found as bacterial cell wall biosynthesis inhibitors. In combination with the above screening, several new antibiotics, nanaomycins, frenolicin B, cervinomycins, asukamycin and so on were discovered as antimycoplasmal substances. Diazaquinomycins as antifolate substance, hitachimycin and avermectin as anthelmintics, herbimycin, phosalacine and oxetin as herbicids have been found by the corresponding each screening system. The structure elucidation, biosynthesis and mode of action of these antibiotics have been studied. Among of them, nanaomycin A and avermectin (or ivermectin) have been employed as antifungal and antiparasitic therapeutics, respectively, for veterinary use.