Kijanimicin (Sch 25663), a novel antibiotic produced by Actionmadura kijaniata SCC 1256. Fermentation, isolation, characterization and biological properties.

Abstract

A novel antibiotic complex has been isolated from the fermentation broth of a new species of Actinomadura, A. kijaniata SCC 1256. The complex was separated from the broth by a solvent extraction procedure and consists of 1 major component, designated kijanimicin, and 3 minor components.Kijanimicin was isolated from the complex by column chromatography and/or preparative high pressure liquid chromatography.Structurally the compound is a unique, large acid enol antibiotic and possesses an unusual in vitro spectrum of activity against some Gram-positive and anaerobic microorganisms.In vivo it has also shown interesting activity against malaria.In the course of our screening for novel antibiotic producing organisms, a culture was noted that appeared distinct in pigmentation from cultures previously observed. This strain, designated SCC 1256, was found to be producing a complex of novel antibiotics from which the major component, designated kijanimicin (Sch 25663) was separated. These antibiotics were active against an unusual spectrum of microorganisms including anaerobes, particulary Propionibacterium acnes. In vivo activity against Plasmodium berghei and P. chabaudi in mice was also observed. This paper details the fermentation and isolation of the antibiotic complex, as well as purification, identification, characterization, 14C labelling, and biological activity of the major component, kijanimicin. Details of the taxonomic evaluation of the producing organism as well as chemical structure elucidation appear elsewhere1-3) . Producing CultureThe producing culture was isolated from a soil sample collected in Kenya. The culture has been identified as a new species of the genus Actinomadura, designated A, kijaniata'~. The strain has been deposited in the American Type Culture Collection, Rockville, Maryland, U.S.A. and has been assigned accession number ATCC 31588. Production of KijanimicinThe medium used for the preparation of the inoculum for antibiotic production consisted of 0.3 beef extract, 0.5% tryptose, 0.1% dextrose, 2.4% potato starch and 0.2% calcium carbonate. The pH of this medium was adjusted to 7.2 prior to sterilization. A 300 ml Erlenmeyer flask containing 70 ml of this medium was inoculated with 5 ml of the stock suspension of the producing strain maintained at -20°C.The flask was incubated at 30°C on a rotary shaker at 250 rpm for 48 hours.

Antitumor Compounds from Actinomycetes in Deep-sea Water of Toyama Bay

“…17.3) were less potent but still showed potent inhibitory activity at 80 nM. [7]), an antitumor antibiotic; chlorothricins (7, [8]), cholesterol biosynthesis inhibitors; versipelostatin (8, [9]), a down-regulator of molecular chaperon GRP78. These compounds are known to be assembled by the polyketide pathway, specifically type I PKS (polyketide synthase) system featured by multifunctional megaenzymes [10].…”

Characterization of the biosynthetic gene cluster for maklamicin, a spirotetronate-class antibiotic of the endophytic Micromonospora sp. NBRC 110955

“…An intriguing point of this group is that the spirotetronate moiety is connected to a trans-decalin system either by a carbonyl unit (for kijanimicin or tetrocarcin A) or by a carboxylic ester (for chlorothricin) (Fig. 1) (Waitz et al 1981;Kawashima et al 1991;Takeda et al 1991). Although the trans-decalin system is also found in versipelostatin A, one of the large-sized spirotetronates comprising a central ring system larger than a 13-membered macrocycle (Park et al 2002), most of the large-sized spirotetronates have no such trans-decalin system.…”

Functional Characterization of Ketoreductase (rubN6) and Aminotransferase (rubN4) Genes in the Gene Cluster of Streptomyces achromogenes var. rubradiris

“…These sugars are formed from simple nucleotide-activated carbohydrates (Kirschining et al 1997). Deoxynitrosugars (DNS) are included in several antibiotics, including rubradirin (Hoeksema et al 1982) (Figure 1), everninomicins (Wagman et al 1964), arugomycin (Kawai et al 1983), viriplanin (Hutter et al 1986), kijanimicin (Waitz et al 1981), and decilorubicin (Ishii et al 1983).…”