Noboritomycins A and B, new polyether antibiotics.

Abstract

NoboritomycinsA and B, two new polycyclic ionophoric polyethers were isolated from a strain of Streptomyces noboritoensis. The crystal structure and absolute configuration of noboritomycin A were established by X-ray analysis of its silver salt C43H63O1,Ag. Noboritomycin A is the first metabolic polyether possessing two carboxylic acid functions on the carbon backbone (C-31), namely a free acid and an additional carboxylic acid ethylestergroup. An unusual spiroketal system as well as a salicylic acid chromophore represent further remarkable elements. Noboritomycin A shows in this respect a structural relationship to salinomycin and lasalocid respectively. Comparison of physico-chemical data, in particular the interpretation of the 1H-and 13C-NMR spectra, revealed that noboritomycins A and B are structurally closely related, noboritomycin B carrying an ethyl substituent on the aromatic ring in the place of a methyl group present in noboritomycin A. Both metabolites exhibit activity against Gram-positive bacteria and against Eimeria tenella (chicken coccidiosis).In the course of our screening for new antibiotics from soil actinomycetes we isolated a strain of Streptomyces noboritoensis (NRRL 8123) which produced two metabolites effective against Grampositive bacteria. The active compounds designated as noboritomycins A and B were characterized as carboxylic acid ionophores and represent new members of the polyether antibiotic group.') This report deals with the taxonomy of the producing strain, as well as fermentation, isolation, structure and biological activities of noboritomycins A and B.

YcaO-Dependent Posttranslational Amide Activation: Biosynthesis, Structure, and Function

“…252 In addition to these standard enzymes, a cytochrome P450 (NosB) is present that carries out the γ-hydroxylation of Glu. 228, 252 This hydroxyl is the site of glycosylation in many other e series thiopeptides, such as glycothiohexide, 314–316 philipimycin, 317 nocathiacin 318, 319 MJ347-81 320 , thiazomycin, 321 and S-54832; 322 however, nosiheptide is naturally an aglycone. Because the primary structural difference between e series thiopeptides is the identity of their sugar (their core peptides vary only by Cys to Ser substitution), nosiheptide is representative of a likely common intermediate that would form during the biosynthesis of these other thiopeptides.…”

A comprehensive review of glycosylated bacterial natural products

“…Currently 21 thiazole glycosides have been reported from different Actinomycetes including Micromonospora , Amycolatopsis , Nocardia, Actinoplanes , and Amycolata . Regiospecificity of glycosylation among the thiazomycin-type members (which includes thiazomycins, 1083,1084 nocathiacins, 1085–1087 glycothiohexides, 1088,1089 philipimycins 1090 and S-54832-A series 1091 ) is restricted to the hydroxyl group of a modified glutamate residue (Glu), the C-4 of a thiazole ring (Thz-3) or a C-3 phenolic substitution of the unique 2,5,6-trithiazolyl-3-hydroxypyridine (Pyr) (Fig. 48).…”

Bioactive heterocycles containing endocyclic N-hydroxy groups

“…N -Hydroxyindole-bearing natural product S-54832/A-I 48a (Table 1), a thiazolyl peptide-based antibiotic, was isolated in 1984 from Micromonospora globosa cultures, and it exhibited excellent growth-inhibiting effect toward Gram-positive bacteria, including Staphylococci, Streptococci, Corynebacteria and Mycobacteria in vitro and against Staphilococcus pyogenes , pneumoniae and S. aureus in vivo [82,83]. N -Hydroxyindoles were also found in nocathiacins I 48b , III 48c and IV 48d in Table 1, a series of antibiotics that were independently isolated by two research groups from bacteria species Nocardia and the fungus Amicolaptosis and they closely resemble the structure of compound 48a [84-86].…”