GERI-155, a new macrolide antibiotic related to chalcomycin.

In the course of screening new antibiotics from soil microorganisms, we have isolated GERI-155 as a new naturally occurring antibiotic. GERI-155 shows anti-microbial activities against Gram-positive bacteria. In addition, two known compounds, chalcomycin1?2) and aldgamycin E3'4), were also detected in the same culture broth. This communication describes the isolation, physico-chemical properties, structure and antibacterial activity of GERI-155 (Fig. 1). The producing organism, Streptomyces sp. GERI-1 55, was isolated from a soil sample collected in Cheolwon-Korean Collection for Type Cultures, under the accession number KCTC-0041BP. The spore suspension of Streptomyces sp. GERI-155 from agar slant culture was inoculated into a seed culture medium. The inoculated flask was shaken on a rotary shaker at 28°C for 48 hours. The seed culture (300ml) was transferred to 30-liter fermenter containing 18 liters of the medium. The seed and production mediumcon-sisted of glucose 2%, soluble starch 1%, meat extract 0.1%, yeast extract 0.4%, soybean meal 2.5%, NaCl 0.2%, and K2HPO40.005%. The pH of the medium was adjusted to 7.3 before autoclaving. The fermentation was continued for 72 hours at 28°C with agitation at a rate of 200rpm and aeration of 20 liters per minutes. The culture filtrate was extracted with ethylacetate. The organic layer was evaporated to dryness in vacuo Fig. 1. Structures of GERI-155 and chalcomycin. 955 and the remaining oily residue was chromatographed on a silica gel column with 1 ~ 50% methanol in chloroform. The active eluate was concentrated and subjected to a Lobar column (Merck, Lichroprep Si 60, Art. 10401, Germany) and eluted with a gradient mixture of chloroform-acetone, from 10: 1 to 1 : 1. Three active fractions were successively eluted containing aldgamycin E (fraction I), chalcomycin (fraction II), and GERI-155 (fraction III). Fraction III was further purified by Sephadex LH-20 column chromatography eluting with acetone, followed by final purification on HPLCusing a reverse phase column (Senshu Pak C18, i.d. 10mm x 300 mm, Japan) eluting isocratically with 55% aqueous methanol. The active eluate was concentrated in vacuo and the resulting aqueous suspension was lyophilized to give 15.9mg of GERI-155 as a white powder. Physico-chemical properties of GERI-1 55 are summarized in Table 1. It is soluble in acetone, methanol, and chloroform, but insoluble in water or hexane. After TLC on silica gel 60 F254 (Merck) with chloroform-acetone (1 : 1), GERI-155 showed an Rf value of 0.21 whereas chalcomycin and aldgamycin E had Rf values of 0.25 and 0.44, …