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Producing Microorganism and Isolation and Characterization of the Antibiotic*

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Producing Microorganism and Isolation and Characterization of the Antibiotic* 452 THE JOURNAL OF ANTIBIOTICS JULY 1971 STUDIES ON ANTIBIOTIC SF-837, A NEW ANTIBIOTIC. I THE PRODUCING MICROORGANISM AND ISOLATION AND CHARACTERIZATION OF THE ANTIBIOTIC* Takashi Tsuruoka, Takashi Shomura, Norio Ezaki, Hiroshi Watanabe, Eiichi Akita, Shigeharu Inouye and Taro Niida Central Research Laboratories, Meiji Seika Kaisha, Ltd. Morooka-cho, Kohoku-ku, Yokohama, Japan (Received for publication March 25, 1971) A new antibiotic, SF-837, having potential utility as a chemotherapeutic agent was discovered in the culture broth of Streptomyces mycarofaciens Shomura and Niida nov. sp. Antibiotic SF-837 is a basic macrolide showing a UV maximum at 232 m//, and is different from the leucomycins, josamycin, the spiramycins and the tertiomycins. It has a molecular formula C41H67NO15 (MW, 813), and liberated 2 moles of propionic acid on hydrolysis. In the continuing search for new antibiotics in this laboratory, a new antibiotic, SF-837, was isolated from the fermentation broth of a Streptomyces strain, which, based on taxonomic study, is considered to be a newspecies, and is namedStreptomyces mycarofaciens nov. sp. Antibiotic SF-837 is active mainly against Gram-positive bacteria, and belongs to the macrolide group. This report deals with the producing microorganism and the isolation and characterization of antibiotic SF-837. Producing Microorganism Streptomyces strain SF-837 which produces antibiotic SF-837 was isolated from soil collected at Onomichi City of Hiroshima Prefecture in Japan. For the taxonomic characterization of strain SF-837, the procedures described by Shirling and Gottlieb2> (supplemented with additional media recommended by Waksman3)) were used. Strain SF-837 shows the following properties : 1. Morphological properties : When grown on media such as glycerine-nitrate agar, glycerine-calcium malate agar, inorganic salts-starch agar (ISP)** and oatmeal agar (ISP), it forms abundant aerial mycelia which develop into manylong coils as shown in Fig. 1. The spores are oval or ellipsoidal, and measure 0.5~0.7x0.8~1.0,u. The surfaces of spores are spiny as shown in Fig. 2. 2. Cultural properties : Cultural properties on various media are listed in Table 1. * A part of this work has been reported in preliminary form.1) ** ISP=International Streptomyces Project. VOL. XXIV -NO. 7 THE JOURNAL OF ANTIBIOTICS 453 Fig1. 1. Aerial mycelium of Streptomyces Fig. 2. Electron micrograph of spores of mycarofaciens, strain SF-837 Streptomyces mycarofaciens, strain SF-837 Table 1. Cultural properties of Streptomyces mycarofaeiens, strain SF-837 M e d iu m G r ow th A e ria l m y c e liu m S o lu b le p ig m e n t S u c r o s e - n itr a te a g a r P o o r , co lo r le ss ~ cr e a m S c a n t, c o tto n y , w h it is h N o n e (2 8 -C ) g r a y G ly c e r in e - n itr a te a g a r D a r k b ro w n W h ite , la te r b e c o m in g - N o n e , o r f a in t lig h t (2 8 -C ) g r a y , c ot to n y b r o w n G lu c o s e - a s p a r a g in e L ig h t b r o w n ~ re d d is h R o s e ~ w h ite N o n e, o r fa in t a g a r (2 8 -C ) b r o w n b r o w n is h y e llo w G ly c e r in e - a s p a ra g in e L ig h t b r ow n ~ lig h t N o n e , o r v e r y sc a n t , N o n e a g a r (IS P ) ( 2 8 -C ) r e d d is h b r ow n w h ite C a - m a la t e a g a r (2 8 -C ) P o o r , c r e a m N o n e N o n e G l y c e r i n e - C a - m a l a t e L i g h t b r o w n R o s e , la te r b e c o m in g N o n e a g a r (2 8 -C ) g r a y , c o tto n y In o rg a n ic s a lts - sta rc h P u rp lish d a r k b r ow n R e d d is h r o s e , la te r N o n e a g a r (IS P ) (2 8 -C ) b e c o m i n g g r a y , c o t t o n y N u tr ie n t a g a r (2 8 -C ) Y e llo w is h b r o w n V e ry s c a n t , w h ite N o n e T y r o s in e a g a r (IS P ) R e d d is h b r o w n W h ite N o n e (2 8 -C ) Y e a s t ex tr a ct -m a lt B r o w n w i t h r e d d i s h W h itis h g ra y N o n e e x tr a c t a g a r (IS P ) t in g e (2 8 -C ) O a tm e a l a g a r (I S P ) G o o d , lig h t b r o w n s A b u n d a n t, ro s e ~ w h it e , N o n e (2 8 -C ) b ro w n la te r b e c o m in g g r ay B e n n e t t 's a g a r (2 8 -C ) B ro w n ~ d ar k b r o w n R o se L ig h t b r o w n P o ta t o p lu g (2 8 -C ) G o o d , th ick , b r o w n t o A b u n d a n t, g r a y ish D a r k b ro w n a lm o s t b la c k b r o w n 3. Physiological properties : Physiological properties, including utilization of carbon sources, are summarized in Tables 2 and 3. From the observations described above, strain SF-837 may be characterized as. follows : It forms coils consisting of chains of spiny-surfaced spores. The color of vegetativejgrowth on synthetic media is cream to brown to reddish brown. Onsome media, thejaerial mass color is rose, later becoming gray and cottony. No distinct <454 THE JOURNAL OF ANTIBIOTICS JULY 1971 diffusible pigment forms on either Table 2. Physiological properties of Streptomyces mycarofaciens, strain SF-837 synthetic or organic media, suggest- P r o d u c tio n o f h y d r o g e n s u lfi d e n e g a tiv e ing that the strain is non-chromo- T y r o s in a s e r ea ct io n n e g a tiv e genic. R e d u c tio n o f n itr a te p o s itiv e 4. Comparison of strain SF-837 C o a g u l a t i o n o f s k i m m e d m i l k p os itiv e P e p t o n i z a t i o n o f s k i m m e d m i l k p os itiv e with related Streptomyces : H y d r o ly s is o f s ta rc h p o s itiv e With respect to the characteristics L iq u e f a ct io n o f g e la tin p o s itiv e ( slo w ) L iq u e f a ct io n o f L o e f f l e r 's c o a g u - n e g a tiv e mentioned above, strain SF-837 has la te d s er u m some similarity to Streptomyces gri- C e llu lo ly t ic a c tiv ity n e g a tiv e seoflavus (Krainsky, 1914) Waksman T e m p e ra t u r e r a n g e (o a t m e a l a g a r ) 1 5 ~ 3 8 -C and Henrici, 19483>5'6\ Streptomyces Table 3. Carbon source utilization of Streptomyces rubiginosus (Preobrazhenskaya et mycarofaciens, strain SF-837 in Pridham and al.) Pridham et al.7>23\ Streptomyces Gottlieb's synthetic agar4> P fasiculatus Pittenger and Nelms ositive utilization glucose, galactose, fructose, mannose, maltose, lactose, in Shirling and Gottlieb 19688) and dextrin, starch, glycerol, inositol, salicin Doubtful utilization OkamiStreptomyceset al.,fungicidicus19549). These(GroupfourG) arabinose,rhamnose Negativexylose,sucrose, raffinose, utilization mannitol, sorbitol, inulin, species and strain SF-837 are similar dulcitol, cellulose in the morphology of their sporo- phores and the spores.
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