Cyanein is a new antibiotic isolated from Penicillium cyaneum by Betina et al.⁵⁾. It posesses a strong anti-HeLa cell activity³⁾, inhibits the growth of the root Allium cepa⁴⁾, and depresses the mitotic activity in the root tips of Vicia Jaba²⁾. It has also an antinematodal activity against Anguillula aceti¹⁾. Cyanein has no antibacterial and antiprototozoal activity but it is active against some pathogenic and nonpathogenic fungi⁵⁾.

In this paper we are presenting results of our study of the activity of cyanein on some yeasts and yeast-like microorganisms, cultivated in media with inorganic and with organic sources of nitrogen.

Culture filtrates of actinomycetes have been screened for the inhibitory activity against growth and glycolysis of Yoshida rat sarcoma cells. From culture filtrates of a strain thus selected, a new antibiotic was isolated and named formycin. As reported in another paper, the formycin-producing strain was classified by Hamada and Okami¹⁾ to Nocardia interforma n. sp.

Formycin shows inhibition against Ehrlich carcinoma, Yoshida rat sarcoma cells and HeLa cells, and also against Xanthomonas oryzae in an ordinary medium and Mycobacterium 607 in a synthetic medium. It shows no inhibition of glycolysis, though this inhibition was observed in the culture filtrate. This paper presents the isolation and characterization of formycin.

Anthelmycin has been obtained from a strain of Streptomyces longissimus found in a soil sample collected in Indiana, U. S. A. This strain of Streptomyces longissimus has been assigned the culture number ATCC-14562.

This paper describes the fermentation, isolation, physical-chemical properties, and the biological activity of anthelmycin; the new antibiotic is of importance because of its anthelmintic activity.

The studies on antitumor antibiotic have been advanced in these ten years, and many antitumor antibiotics were isolated from Streptomyces species. Among them, macromolecular substances which were reported as polypeptide or protein in nature, are gannmycin^1,2), carzinocidin^3～7), melanomycin^8,9), peptimycin¹⁰⁾, actinogen¹¹⁾, A-216 substance^12,13), A-280 substance^12,13) and enomycin ¹⁴⁾.

In our laboratory, antitumor activities of culture filtrates of strains of Streptomyces have been tested using experimental animal tumors. In 1959 a strain of Streptomyces No. B-2771 was isolated from a soil sample obtained at Minamiuwa-gun, Ehime Prefecture. Microbiologically, this strain was found to be different from any species reported previously and named Streptomyces phaeoverticillatus nov. sp.¹⁵⁾

We found that the culture filtrates of this new strain of Streptomyces inhibited the growth of Ehrlich ascites carcinoma, prolonging the survival time of host animals remarkably. A new antitumor substance was isolated from the culture filtrates of this strain and was designated as iyomycin.

A partially purified iyomycin preparation obtained from the culture filtrates by a precipitation method in our preliminary experiment, inhibited the growth of ascitic form of Ehrlich carcinoma and sarcoma 180, and prolonged the life span of the treated mice. Futhermore, it was found later that several active fractions existed not only in the culture filtrate but also in the mycelium. The extractions and purifications of active components were therefore carried out.

The present paper describes the production and extraction, physico-chemical and biological properties of iyomycin complex containing iyomycin A as a main component which showed properties of a macromolecular substance.

A strain of Streptomyces No. B-2771 was isolated from a soil sample obtained in the vicinity of Kanjizai temple, Gosho-machi, Uwa-gun, Ehime Prefecture in 1959. This strain exhibited an anticancer activity in our screening program of anticancer substances. Culture filtrates of the strain injected intraperitoneally once or several times prolonged survival period of mice bearing Ehrlich ascites carcinoma by more than 30 days and prevented some of mice from death.

Characteristic changes in the ascites tumor cells appeared within 48 to 72 hours following the intraperitoneal injection of the filtrate.

The active substance obtained from the culture filtrates was proved to be a new substance and was given a name of iyomycin¹⁾.

The strain of Streptomyces No. B-2771, produced aerial hyphae with primary and secondary whirls, when cultured on several media for Streptomyces. The morphological, cultural and physiological characteristics were considered sufficiently unique to differentiate this strain from other known species of Streptomyces. Thus, the strain No. B-2771 was established as a new species and given a name of Streptomyces phaeouerticillatus n. sp.

As reported in the previous paper, Nomura et al.¹⁾ found that a strain of Streptomyces produced an antitumor substance which was very effective on Ehrlich ascites carcinoma in mice. This antitumor agent was designated as iyomycin. The iyomycin-producing strain was isolated from a soil sample obtained at Ehime Prefecture in Shikoku Island in Japan and assigned to be a new species, Streptomyces phaeoverticillatus.

The iyomycin was purified as a black lyophylized and non-dialyzable powder, and was considered a macromolecular substance. As a result of further studies, however, it was confirmed that the iyomycin contained several components possessing antitumor activity, and we generally named them “iyomycin complex”.

The iyomycin complex was roughly classified into A and B, and B was subdivided into B₁, B₂, B₃, B₄, and B₅. Iyomycin A is an acidic macromolecular substance which will be reported in a separate paper³⁾. Iyomycin B is a general name of substances which exhibited a dialyzable basic property and obtained from the iyomycin complex and/or the culture broth of iyomycin-producing strain. Among the components of the iyomycin complex, B₁ exhibited the highest antitumor activity.

In this paper, isolation and properties of the iyomycin B group substances are presented.

Formycin¹⁾ has been isolated from culture filtrates of Nocardia interforma on the basis of the activity against Yoshida rat sarcoma cells in tissue culture. The purified formycin inhibited Yoshida rat sarcoma cells and HeLa cells, but it showed no inhibition against glycolysis of the former cells. Tnis antibiotic was found to inhibit Mycobacterium 607 and the inhibitory effect was antagonized by constituents in peptone-meat extract medium. Labilomycin inhibiting Gram positive bacteria was isolated from Streptomyces albosporeus var. labilomyceticus²⁾ and the hydrolyzed product, labilose, was determined to be 6-deoxy-2, 4-di-O-methyl-D-galactose³⁾. The present authors found that this antibiotic had weak inhibition against Ehrlich ascites tumor. Results of testing these antibiotics for their effect against HeLa cells, Yoshida rat sarcoma cells, and ascites type of Ehrlich carcinoma are described in this paper.