An actinomycete strain No. Q996-17 produced a novel compound, epoxomicin, which exhibited in vivo antitumor activity against B16melanoma. Structural studies indicated that it is a newmember of the epoxy-jS-aminoketonegroup, and is closely related to eponemycin.In our continuous search for antitumor agents showing specific activity against B16 murine melanoma, an unidentified actinomycete strain No. Q996-17 was found to produce a new compound epoxomicin. It wasextracted by rc-butanol from the fermentation broth and purified by various chromatographies. Structural studies revealed that epoxomicin has an epoxy-^-aminoketone moiety in the structure and is a newmemberof the eponemycin^group. Epoxomicin exhibited strong in vitro cytotoxicities against various tumor cell lines, whereas it did not exhibit anti-bacterial and anti-fungal activities. It showed strong in vivo inhibitory activity against B16 melanoma but moderate activity against P388 mouse leukemia.

Streptomyces amphibiosporus R310-104 (ATCC53964) produced a novel antibiotic lactimidomycin which showed inhibitory activity against fungi and prolonged the survival time of mice transplanted with experimental tumors. Structural studies clarified that lactimidomycin is a new glutarimide antibiotic having a unique unsaturated 12-memberedlactone ring.In the course of screening for new antibiotics effective against experimental tumors, we have isolated a novel antibiotic designated lactimidomycin from the culture broth of Streptomyces amphibiosporus R310-104 collected in Akita city1'2*. The antibiotic exhibited strong cytotoxicity against various tumor cells and inhibitory activity against fungi but no antibacterial activity. It demonstrated prolongation of life span in mice bearing P388 leukemia and B l 6 melanoma. The structure oflactimidomycin was determined by spectroscopic analyses and 13C-enriched biosynthetic studies to be a novel glutarimide group antibiotic having a unique 12-memberedlactone ring as a side chain.In this paper, we describe the production, isolation, physico-chemical properties, structure determination and biological activity of lactimidomycin. Antibiotic Production A loopful mature slant culture of S. amphibiosporus R3 10-104 was inoculated into 100 ml of vegetative mediumconsisting of soluble starch (Nichiden Kagaku) 2%, Pharmamedia(Traders Protein) 1%, ZnSO4-7H2O0.003% and CaCO3 0.4% in a 500-ml Erlenmeyer flask (pH 7.0 before sterilization).The flask was incubated at 32°C for 7 days on a rotary shaker (200rpm) and 5 ml of vegetative inoculum was added to 100ml of sterile production medium containing Protein-S (Ajinomoto Co.) 3%, glucose 3%, Pharmamedia 0.5%, yeast extract (Oriental Yeast Co.) 0.1% and CaCO3 0.3%, pH 7.0 in a 500-ml Erlenmeyer flask. The flask was incubated at 28°C on a rotary shaker (200rpm). Antibiotic production was monitored by the in vitro cytotoxicity against B16 melanomacells and it reached maximumafter 4 days incubation. Isolation and PurificationThe fermentation broth (18 liters, pH 7.4) was stirred with 1-butanol for one hour. The solvent layer was separated from the aqueous layer and mycelial cake by use ofa Sharpies type centrifuge and concentrated under reduced pressure. The residue (30 g) was suspended in water (1 liter) and extracted three times with Lactimidomycin was originally called as BU-4146T or BMY-28886.

Streptomyces hygroscopicus No. P247-7 1 (ATCC53709) produced a novel antibiotic eponemycin which exhibited specific in vivo antitumor effect against B 16 melanoma.Structural studies assigned {AS)-1 ,2-epoxy-2-hydroxymethyl-4-(7V-isooctanoyl-L-serylamino)-6-methylhept-6-ene-3-one to eponemycinwhichis unrelated to the knownantitumor antibiotics.In our continuing search for new microbial metabolites with antitumor activity, Streptomyces hygroscopicus No. P247-71 , isolated from a soil sample from the Philippines, was found to produce a novel antibiotic with specific activity against B16 melanoma. The active principle, eponemycin, was recovered from the fermentation broth with ethyl acetate extraction and purified by chromatography. Structural studies revealed it to be a novel molecule composedof isooctanoic acid, L-serine and an aminoepoxyketone. 9-Methylstreptimidone wasisolated as a co-product from the crude extract.Eponemycin showed potent growth inhibition against various tumor cells, but no inhibitory activity against bacteria and fungi. It induced significant prolongation of survival time of mice transplanted with B16 melanoma, while no antitumor activity was observed against P388 leukemia.In this paper, we describe the production, isolation, physico-chemical characterization, structural elucidation and biological properties of eponemycin.Taxonomy of the Producing Strain Source of Organism Strain P247-71 was isolated from a soil sample collected near the root of a tamarind at Mt. Apo, Davao, Mindanao Island, Philippines. MorphologyBoth substrate and aerial mycelia are formed. They are long, well-branched and not fragmented into short filaments. Chains ofarthrospores are born on the aerial hyphae. The spore chain and spore morphology are as follows: 1) Spiral spore chains with 2 to 8 turns, 2) monopodially branched sporophores, 3) spores, oval or barrel-shaped (0.5 to 0.7 by 0.5 to 1.2/mi), and 4) spore ornamentation, rugose or smooth.Sporangium, motile spore and sclerotium are not observed. Cultural and Physiological CharacteristicsStrain P247-71 grows well in most descriptive media. Gray aerial mycelium with hygroscopic black patches is observed on International Streptomyces Project (ISP) agar media except for ISP No. 6 medium.Eponemycin was originally designated BMY-28647 or BU-3862T.

Quinaldopeptin, a new type of quinomycin antibiotic, was isolated from the culture of Streptoverticillium album strain Q132-6. The antibiotic exhibited strong in vitro antimicrobial and cytotoxic activity and significantly prolonged the survival time of mice inoculated with a murine tumor. Quinaldopeptin is a symmetric cyclic peptide linked only by peptide bonds and differs from known antibiotics of the quinomycin family by the lack of ester linkage.In our search for microbial metabolites with antitumor activity, a novel antibiotic, quinaldopeptin has been isolated from the cultured broth of Streptoverticillium album strain Q132-6 which was isolated from a soil sample collected in AndhraPradesh, India. The antibiotic was recovered from the fermentation broth by solvent extraction and purified by chromatography. Structural studies combining spectral analysis and chemical degradation disclosed that quinaldopeptin is a symmetric cyclic peptide comprised of 2 mol each of 3-hydroxyquinaldic acid, glycine, sarcosine and a,/?-diaminobutyric acid and 4mol of pipecolic acid. Although quinaldopeptin should be classified in the quinomycin group of antibiotics, it distinctly differs from the known compounds by the lack of an ester linkage. Quinaldopeptin is highly active against Gram-positive bacteria and anaerobes and strongly cytotoxic against cultured B16melanomacells. It prolonged the survival time of mice transplanted with P388 leukemia. This paper describes the isolation, properties, structural determination and biological activities of quinaldopeptin.

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