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Aclacinomycin A and B, two major components of a new antitumor antibiotic complex, and their 19 analogues were produced by a culture of strain No. MA144-Ml, which was identified as Streptomyces galilaeus. They were isolated by chelation with copper ion and silicic acid chromatography, and characterized by physicochemical methods in the anthracycline group of antibiotics. During the course of screening for new antitumor antibiotics, the cultured broth of an organism MA144-M1, which was isolated from a soil sample collected in Kamiosaki, Shinagawa-ku, Tokyo, Japan, showed marked inhibitory effect on L1210 leukemia in mice. The organism produced a new water-insoluble pigment antibiotic complex named aclacinomycin, which was extracted from the cultured broth and separated into thirteen yellow and seven red-colored components. They belong to the aklavinone and e-pyrromycinone group of anthracyclines, and aclacinomycins A and B1) were produced preferentially. The results of structural studies2~4) indicated that twelve components; Al (aclacinomycin A), BI (aclacinomycin B), Y1 (aclacinomycin Y), Ll (N-monodemethyl aclacinomycin A), G1 (MA144 G1), M1 (MA144 Ml), N1 (MA144 NI), S1 (MA144 S1), TI (1-deoxypyrromycin), El (7,7'-dideoxy-7,7'-biaklavinone), M2 (MA144 M2), and S2 (MA144 S2) were confirmed to be novel compounds. Three yellow components, Cl, D1 and Fl, and five red-colored components, A2, B2, T2, C2 and D2 were identical with 7-deoxyaklavinones), aklavinones"'), bisanhydroakla-vinone7), cinerubin A8), cinerubin B9), pyrromycin10), 7-deoxypyrromycinone (~-pyrromycinone)5), and e-pyrromycinone10), respectively. This paper deals with the taxonomy of the producing organism, the production, isolation and physicochemical properties of aclacinomycin A and its analogues. Taxonomy (1) The Strain MA144-M1 has the following morphological characteristics: Open spirals were observed to develop well from branched substrate mycelia. There were no whorls, and mature spore

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Anthracyclineantibiotics aclacinomycins (ACMs) are aklavinone glycosides with variation in the trisaccharide moiety and were produced by Streptomyces galilaeus MA144-M1. Their production" and structural elucidation') were previously reported. By the isolation of various mutants') and the conversion of hypothetical precursors fed in the cultural medium'), we found that ACMs were formed by a step-wise glycosidation of aklavinone followed by enzymatic modification of the terminal sugars). We report here the 11C NMR study of the biosynthesis of aklavinone by the incorporation of "Cacetate and "C-propionate and the radioisotopic analysis of ACM labeled with 14C-precursors.For the incorporation experiments, a blocked mutant strain 3AR-33, which accumulated aklavinone by the genetic loss of glycosidation ability'), and an aclacinomycin A (ACM-A) producing strain 6U-213) were inoculated into a 500-m1 Erlenmeyer flask containing 50 ml of productive medium consisting of 1.5 % potato starch, 1.0 % glucose, 3.0 % soybean meal (Meat, Ajinomoto Co.), 0.1 % yeast extract, 0.3 NaCI, 0.1 % KZHPO4, 0.1 % MgSO4.7H2O, 0.0007 ; CuSO4.5H2O, 0.0008 % MnCl2.4H,O, 0.0002 % ZnSO4.5HZO and 0.0001 % FeSO4 7HZO, pH 7.41). During a rapid productive phase of antibiotic (around 20 35-hour cultivation), each 13C-or "C-labeled compound was added to the culture and the cultivation at 28°C on a rotary shaker (220 rpm) was continued for one to 20 hours. The cultured broth was then harvested and centrifuged. The crude antibiotic was extracted from the mycelium with acetone and froth the supernatant fluid with chloroform. The isolation and purification of aklavinone and ACM-A from the extracts were performed by preparative layer chromatography using silica gel 60 PF25} (E. Merck) according to the method previously described 2). Solvent systems used were CHCI3 -MeOH (50: 1) for aklavinone and CHCI, -MeOH (20: 1) for ACM-A.