A83586C, a new depsipeptide antibiotic.

Abstract

A culture identified as Streptomyces karnatakensis was found to produce a novel cyclic hexadepsipeptide antibiotic designated A83586C.The structure was elucidated by X-ray crystallography, and full XHand 13CNMR assignments are reported. The absolute configuration was confirmed by the detection of D-threonine in the acid hydrolysate of A83586C. A83586Chad potent Gram-positive activity in vitro but lacked in vivo efficacy in mice.During the course of screening for biologically active metabolites, culture A83586, subsequently identified as a strain of Streptomyces karnatakensis, was isolated. This culture, which produced a complex of piericidins0, was also found to produce an antibiotic possessing potent Gram-positive activity. Isolation of this antibiotic, designated A83586C, yielded a crystalline material which was shown by X-ray analysis to be a cyclic hexadepsipeptide closely related to azmothricm2). The absolute stereochemistry was determined to be the same as in azinothricin through the detection of D-threonine in an acid hydrolysate of A83586C. In fact, A83586C differs from azinothricin only in the presence of iV-hydroxy-L-alanine instead of iV-hydroxy-O-methyl-L-serine, and in having a methyl instead of an ethyl group at C-37. Other antibiotics containing the piperazic acid moiety include the monamycins3), and PD 124,9664) (C. D. Rithner; personal communication). TaxonomyCulture A83586 was isolated from a soil collected in Guam. The culture was characterized following methods outlined by the International Streptomyces Project (ISP)5). ISCC-NBS Centroid Color Charts, standard sample No. 2106 and the Color Harmony Manual (4th Ed., 1958, Container Corporation of America, Chicago, Illinois) were used to identify the colors of the reverse side and aerial spore mass respectively.The culture grew well on both complex and defined media. Aerial spore mass color was predominantly gray, although some white and pale yellow were observed. The reverse color was yellowish brownto grayish yellow. Soluble pigments were not produced. The cultural characteristics of A83586 on various ISP media are presented in Table 1.The culture A83586 produces an extensive substrate mycelium. Aerial hyphae produce long, compact chains of spores arranged in spirals consisting of 5 or more coils. There are > 10 spores per chain. The spore surface is covered with long profuse hairs (Fig. 1). Thus the morphology is spiral (S) and spore surface hairy (HA).Culture A83586is characterized by a very narrow carbohydrate utilization pattern. It utilized the following carbohydrates : D-Galactose, glucose, glycerol, glycogen, maltose, mannose, D-trehalose, and sodium butyrate. It was unable to utilize adonitol, d-and L-arabinose, cellobiose, cellulose,

Kettapeptin: Isolation, Structure Elucidation and Activity of a New Hexadepsipeptide Antibiotic from a Terrestrial Streptomyces sp.

“…The search with these spectroscopic data in AntiBase [9] did not reveal a structure that matched the NMR data, the molecular weight and the empirical formula of 1. However, the search uncovered hexadepsipeptides with similar analytical data: azinothricin [1] (2), A83586C [10] (3), GE3 (4) [2] and citropeptin [11] (5). The similarity of the NMR data with those of 2ϳ5 indicated that the isolated compound might be a related cyclopeptidelactone.…”

Paradigm Shifts in Fungal Secondary Metabolite Research: Unusual Fatty Acids Incorporated into Fungal Peptides

“…A culture identified as Streptomyces karnatakensis was found to produce a cyclic hexadepsipeptide antibiotic designated A83586C. A83586C had potent Gram-positive activity in vitro, but lacked in vivo efficacy in mice (Smitka et al, 1988), and also contained FA [155].…”

A New Depsipeptide Antibiotic, Citropeptin

“…The structure of this antibiotic was elucidated by NMR spectral analysis to be a cyclic hexadepsipeptide closely related to azinothricinl) and A83586C. 2 ) This paper describes the taxonomy of the producing organism and the fermentation, isolation, physicochemical properties and biological activity of citropeptin. …”