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A precursor of biphenomycin A in mixed culture of Streptomyces griseorubiginosus No. 43708 with Pseudomonas maltophilia No. 1928 was isolated and characterized. The structure of the precursor, designated biphenomycin C was determined to be a peptide which is composed of biphenomycin A and arginylserine residue (Fig. 1), on the basis of chemical and spectroscopic evidence.

Streptomyces griseoflavus, a bicozamycin-producing wild type strain and its high-producing one derived from it by multiple (greater than 15) mutagenic treatments, were analyzed physiologically and biochemically. The high-producing strain was characterized by: (1) An increased pool size of amino acids including leucine and isoleucine, precursors for bicozamycin synthesis, (2) an earlier and greater accumulation of intracellular ppGpp, (3) a more accentuated decrease in GTP pool size, (4) a higher specific activity of ornithine transcarbamylase which produces citrulline, (5) an increased ability to form aerial mycelium, and (6) an increased resistance to its own antibiotic. We propose that (1), (2) and (4) may be responsible for the high yields of bicozamycin and, possibly, of some other antibiotics produced by Streptomyces sp.

Biphenomycin A, C23H28N4O8, and biphenomycin B, C23H28N4O7, were isolated from the cultured broth of Streptomyces griseorubiginosus No. 43708. The antibiotics are active in vitro and in vivo against bacteria, and are especially potent against Gram-positive bacteria. The acute toxicity of biphenomycin A is very low in mice.

New vasodilators, designated WS-1228 A and B have been discovered in the culture filtrate of a strain of Streptomyces aureofaciens. The active compounds were purified by column chromatography with Diaion HP-20 and silica gel, and finally separated from each other by high performance liquid chromatography. They were obtained as pale yellow crystals and their molecular formulae were both C11H17N3O.

WF-5239 was produced by a fungal strain identified as Aspergillus fumigatus Fresenius. The substance was purified by solvent extraction followed by chromatography on silica gel and then crystallized (C9H9NO2, mp 142 approximately 145 degrees C). The chemical structure was determined from its physico-chemical properties as N-[2-cis(4-hydroxyphenyl)ethenyl]formamide. WF-5239 has inhibitory activity against rabbit platelet aggregation induced by arachidonic acid and collagen, with IC50 values of 1.25 and 5.0 micrograms/ml, respectively. Arachidonic acid induced mortality in mice was reduced by a single intraperitoneal dose of WF-5239 (30 mg/kg). These biological properties have been compared with those of aspirin.

WF-3161 is an antitumor antibiotic produced by a strain of fungus, Petriella guttulata. The antibiotic was purified by solvent extraction and a combination of silica gel and reverse phase column chromatography. The chemical structure of the antibiotic (C31H44N4O6, mp 181-183 degrees C) was found to be a cyclic tetrapeptide consisting of phenylalanine, leucine, pipecolinic acid and 2-amino-8-oxo-9,10-epoxydecanoic acid. WF-3161 inhibited the growth of Trichophyton asteroides. It prolonged survival period of mice bearing leukemia P-388 with a high therapeutic index.

WS-30581 A and B are antiplatelet agents produced by a strain of Streptoverticillium waksmanii. The compounds were purified by solvent extraction and column chromatography, and identified as new pimprinine analogs on the basis of their physico-chemical properties. The producing organism produced pimprinine along with these compounds. Pimprinine and the two new analogs have potent inhibitory effects on platelet aggregation.