Avidinorubicin(MW 1,214, C60H86N4O22) was isolated from the cultured broth of strain
NR0576(which was identified as Streptomyces avidinii Stapley et al.) by butyl alcohol extraction,Sephadex LH-20 column chromatography and preparative HPLC. Avidinorubicin inhibited thrombin-induced platelet aggregation with an IC50 being 7.9 umand was determined to be a novel anthracycline possessing two units ofa new aminosugar, avidinosamine, in place of two decilonitrose groups in decilorubicin.
635In the course of our screening for unique microbial products with pharmacological activity, avidinorubicin (1) that exhibited platelet aggregation inhibitory activity was isolated from the cultured broth of Streptomyces avidinii. Avidinorubicin was considered to belong to the nogalamycin1* group based on the presence of a unique anomeric proton in the 1H NMRspectrum. After spectral analyses, avidinorubicin was determined to be a novel anthracycline containing two units of a newaminosugar, avidinosamine. This paper describes the taxonomy,fermentation, isolation, physico-chemical properties and structure elucidation of avidinorubicin.Fermentation The producing strain of avidinorubicin, NR0576, was isolated from a soil sample collected at Komono-cho, Mie Prefecture, Japan and identified as S. avidinii Stapley, Mata, Miller, Demnyand Woodruff2). A spore suspension of this strain (0.2ml) was inoculated into a 500-ml baffled Erlenmeyer flask containing 100ml of a medium consisting of glucose 2.0%, potato starch 2.0%, yeast extract 0.5%, toasted soya 2.0%, NaCl 0.25%, ZnSO4-7H2O 0.005%, CuSO4-5H2O 0.0005%, MnCl2 -4H2O 0.0005%, CaCO3 0.32% and Nissan Disfoam 0.05%. The medium was adjusted to pH 7.0 before addition ofCaCO3. The inoculated flask was incubated on a rotary shaker at 27°C for 3 days at 190rpm to make a seed culture. The resultant seed culture (12 ml) was transferred into a 3-liter baffled Erlenmeyer flask containing 600ml of the same mediumfollowed by incubation on a rotary shaker at 27°C for 3 days at 100rpm. This seed culture (600ml) was transferred into a 200-liter jar fermenter containing 120 liters of the same medium. The cultivation was carried out at 27°C for 6 days, agitated at 280rpm and aerated at 150 liters per minute.