New glutarimide antibiotics, S-632-B1 and B2. II. Isolation, physico-chemical properties and chemical structure

Antifungal antibiotics S-632-A1,A2,B1 and B2 were extracted with ethyl acetate from the filtered broth of Streptomyces hygroscopicus S-632 and isolated through a combination of conventional and reversed-phase silica gel column chromatography. On the basis of the spectral data, S-632-B1 and B2 were found to be new members of the glutarimide family of antibiotics. The chemical structures of these components were elucidated as two stereo-isomers of 3-(5,7-dimethyl-8,9-epoxy-2-hydroxy-4-oxo-6-decenyl)glutarimide.     

TPU-0031-A and B, new antibiotics of the novobiocin group produced by Streptomyces sp. TP-A0556

Two novel antibiotics, TPU-0031-A and B, were isolated from the culture broth of an actinomycete strain. The producing strain, TP-A0556, was identified as Streptomyces sp. based on the taxonomic study. The new antibiotics were obtained by solvent extraction and chromatographic purification. Spectroscopic analyses showed that TPU-0031-A and B were 7'-demethylnovobiocin and 5"-demethylnovobiocin, respectively. These compounds showed antibiotic activity against Gram-positive and -negative bacteria.     

Clethramycin, a new inhibitor of pollen tube growth with antifungal activity from Streptomyces hygroscopicus TP-A0623. I. Screening, taxonomy, fermentation, isolation and biological properties

The cytoskeletal proteins, actin and myosin, play a central role in pollen tube growth. The pollen tube growth is inhibited by cytochalasin, which interferes with actin polymerization. In the screening of pollen tube growth inhibitors, clethramycin was found from the fermentation broth of an actinomycete strain TP-A0623. The producing strain was isolated from a root of Clethra barbinervis collected in Toyama, Japan and identified as Streptomyces hygroscopicus based on the taxonomic study. Clethramycin showed in vitro antifungal activity against yeast such as Candida albicans and C. glabrata with the MIC of 0.5 approximately 8 microg/ml, but weak activity against Gram-positive and negative bacteria (MIC > or = 64 microg/ml). Cytotoxicity of clethramycin was moderate and the IC50 was 57 microg/ml against HeLa cells and 120 microg/ml against WI-38 cells.     

Inosamycin, a complex of new aminoglycoside antibiotics. I. Production, isolation and properties

A strain of Streptomyces hygroscopicus No. J296-21 (ATCC 39150) was found to produce a complex of new antibiotics, called inosamycins, which consisted of components A, B, C, D and E. They are novel aminocyclitol antibiotics structurally related to neomycin, paromomycin and ribostamycin. The antibiotic complex and each component of inosamycin exhibit a broad antibacterial spectrum but they are inactive against most of the aminoglycoside-resistant organisms. The antibacterial activity of inosamycin A, the major component of the complex, is comparable to that of neomycin but its acute toxicity is significantly lower (ca. 1/3) than that of neomycin.     

New antitumor antibiotics, OS-4742 A1, A2, B1 and B2 produced by a strain of Streptomyces

New antibiotics, OS-4742 A1, A2, B1 and B2, were isolated from the culture broth of the strain OS-4742, which was designated as Streptomyces matensis subsp. vineus. These compounds have anthracycline chromophores and sugar moieties, but do not contain nitrogen. They possess antimicrobial activities against Gram-positive bacteria and antitumor activities against S-180 solid tumor on mice.     

假轮枝链霉菌Streptomyces pseudoverticillus产生的elaiophylin类新细胞周期抑制剂及细胞凋亡诱导剂I.菌种鉴定、发酵生产及提取分离

从链霉菌YN17707菌株发酵物中,通过活性跟踪分得三个elaiophylin类新细胞周期抑制剂及细胞凋亡诱导剂elaiophylin、11-O-monomethylelaiophylin和efomycin G。经菌种分类学研究,生产菌YN17707被鉴定为假轮枝链霉菌Streptomyces pseudoverticillus,并认证为elaiophylin类的新生产菌种。文中还探讨了该生产菌发酵生产elaiophylin类活性成分的发酵特征。     

Watasemycins A and B,new antibiotics produced by Streptomyces sp. TP-A0597

Two novel antibiotics, watasemycins A and B, were isolated from the fermentation broth of an actinomycete strain. The producing strain TP-A0597 was isolated from the seawater sample collected in Toyama Bay, Japan and identified as Streptomyces sp. based on the taxonomic study. The new antibiotics were obtained by solvent extraction and chromatographic purification and spectroscopic analyses identified that they were new analogs of thiazostatins. Watasemycin possesses a methyl group at 5'-position of thiazostatin instead of a hydrogen atom. Watasemycins showed antibiotic activity against Gram-positive and negative bacteria and yeast.     

Antibiotic A-130, isolation and characterization.

An antibiotic, A-130, was isolated from a strain identified as Streptomyces hygroscopicus, strain A-130. The antibiotic belongs to the nigericin group and like dianemycin, has an alpha, beta-unsaturated ketone chromophore in its molecule. A-130 is active against gram-positive organisms.     

Isolation and characterization of novel geldanamycin analogues

New geldanamycin analogues with novel structures arising from direct microbial bioconversion and a genetically engineered geldanamycin producer were isolated and characterized. Three compounds, 15-hydroxygeldanamycin, a tricyclic geldanamycin analog (KOSN-1633), and methyl-geldanamycinate), were isolated after geldanamycin was added to a growing culture of the herbimycin producing strain-Streptomyces hygroscopicus AM-3672. Two related compounds, 17-formyl-17-demethoxy-18-O,-21-O-dihydrogeldanamycin and 17-hydroxymethyl-17-demethoxygeldanamycin were isolated from S. hygroscopicus NRRL 3602/pKOS279-78, a geldanamycin-producing strain containing various genes isolated from S. hygroscopicus AM-3672. Compared with geldanamycin, these five new compounds exhibited reduced cytotoxicity against SKBr3 cancer cells.     

新型强效免疫抑制剂西罗莫司F904的研究

从福建省福州市的土壤中分离到的链霉菌 FC90 4 ,经分类鉴定、菌株培养确定为吸水链霉菌。其发酵代谢产物 F90 4具有抗真菌、抗增殖和比环孢素强的免疫抑制活性。分离、纯化、结晶 ,得 F90 4 ,经理化性质、光谱分析和 X-射线单晶衍射研究证明 F90 4为三烯大环内酯新型强效免疫抑制剂西罗莫司。     

Arisostatins A and B, new members of tetrocarcin class of antibiotics from Micromonospora sp. TP-A0316. I. Taxonomy, fermentation, isolation and biological properties

Arisostatins A and B, new members of tetrocarcin class of antibiotics were isolated from the culture broth of an actinomycete strain. The producing strain, TP-A0316, was identified as Micromonospora sp. Arisostatins were obtained from the culture fluid by solvent extraction and chromatographic purification. They showed antibiotic activity against Gram-positive bacteria and antitumor activity.     

吸水链霉菌应城变种质粒的分离研究

采用蔗糖浓度为13％的YEME培养基培养吸水链霉菌应城变种10-22菌株,能获得生长量较高且分散状况良好的菌丝体。在探索链霉菌质粒DNA的分离方法时,以T.Kieser的方法为基础,提高国产溶菌酶的用量和延长酶解时间,首次从吸水链霉菌应城变种中分离到一种质粒DNA分子,将它命名为pSH_(47)。同时,通过pock形成能力的检测。进一步证实这个质粒的存在。吸水链霉菌应城变种10-22菌株经吖啶橙处理后获得的部分或全部丧失5102抗生素生物合成能力的几个阻遏突变株的质粒检测结果表明,它们都有与10-22菌株相同的质粒带。     

Isolation, structure determination and biological activity of a new glutarimide antibiotic, S632A3

A new antibiotic, S632A3, was isolated from a cultured broth of Streptomyces hygroscopicus S632. It was purified by column chromatography on silica gel, Sephadex LH-20 and HPLC. Structural studies by analysis of 1H NMR and 13C NMR, MS, UV and IR spectra in comparison with those of S632A2 clarified that S632A3 is an isomer of 9-methylstreptimidone. In addition, this antibiotic showed potent biological activity including differentiation induction effects on HL-60 cell and antitumour activity in vivo.     

Alahopcin, a new dipeptide antibiotic produced by Streptomyces albulus subsp. ochragerus subsp. nov

An actinomycete strain No. B-52653 was found to produce an antibiotic selectively active against the in vitro antibiotic resistant mutant of Staphylococcus aureus. Based on taxonomic studies, the name Streptomyces albulus subsp. ochragerus subsp. nov. is proposed for the strain. The microorganism produced two kinds of antibiotics; one identical with gougerotin, the other an amphoteric water soluble dipeptide containing L-alanine. The latter has the molecular formula C9H15N3O6 and is named alahopcin. It has a broad antibacterial spectrum and a synergistic effect with some other antibiotics against some antibiotic resistant staphylococci. Alahopcin has a low toxicity and was effective against experimental infections in mice caused by Staphylococcus aureus.     

TPU-0037-A,B, C and D,novel lydicamycin congeners with anti-MRSA activity from Streptomyces platensis TP-A0598

In screening for anti-MRSA antibiotics, novel lydicamycin congeners, TPU-0037-A, B, C and D, were isolated from a culture broth of an actinomycete strain. The producing strain, TP-A0598, was isolated from a seawater sample collected in Toyama Bay, Japan, and identified as Streptomyces platensis based on taxonomic characteristics. TPU-0037-A, B, C and D were purified by HP-20 resin, ODS column chromatographies and preparative HPLC, consecutively, and their structures were determined to be 30-demethyllydicamycin, 14,15-dehydro-8-deoxylydicamycin, 30-demethyl-8-deoxylydicamycin and 8-deoxylydicamycin, respectively, by NMR and MS analyses. The new congeners showed antibiotic activity against gram-positive bacteria including MRSA with the MIC of 1.56 to approximately 12.5 microg/ml.     

Septamycin, a polyether antibiotic. Taxonomy, fermentation, isolation and characterization.

Septamycin is a metal complexing polyether antibiotic produced by a strain of Streptomyces hygroscopicus NRRL 5678. The metabolite, a monocarboxylic acid, was isolated as the sodium salt C48H81NaO16. The crystal structure and absolute configuration were established by X-ray analysis of the p-bromophenacyl derivative. Septamycin has a thirty-carbon backbone and contains seven heterocyclic rings. Supported by direct comparison septamycin proved to be identical with antibiotic A28695 A isolated from Streptomyces albus NRRL 3883. The metabolite is active against gram-positive bacteria and Eimeria tenella (chicken coccidiosis).     

Milbemycins, a new family of macrolide antibiotics. Studies on the biosynthesis of milbemycins alpha 2, alpha 4 and D using 13C labeled precursors

The biosynthetic origins of the carbon skeleton of milbemycins alpha 2, alpha 4 and D were studied. 13C Labeled antibiotics, milbemycins alpha 2, alpha 4 and D, were isolated from the culture broth of Streptomyces hygroscopicus subsp. aureolacrimosus strain Au-3 after feeding [1-13C]acetate, [1-13C]-propionate, [3-13C]propionate, [1-13C]isobutyrate, DL-[2-13C]valine and L-[methyl-13C]methionine, and 13C NMR spectra of the antibiotics thus obtained were measured. It was revealed that the carbon skeleton, except for carbon 25, of milbemycins alpha 2, alpha 4 and D are derived from seven acetate units and five propionate units. It was also shown that the methyl, ethyl and isopropyl groups at carbon 25 in milbemycins alpha 2, alpha 4 and D are derived from acetate, propionate and isobutyrate or DL-valine, respectively, and the methyl carbon of the methoxy group at carbon 5 in milbemycins alpha 2 and alpha 4 was enriched by L-[methyl-13C]methionine.     

Arizonins, a new complex of antibiotics related to kalafungin. I. Taxonomy of the producing culture, fermentation and biological activity

The arizonins, a novel complex of antibiotics related to kalafungin, were discovered in the fermentation broth of Actinoplanes sp. AB660D-122. Comparative taxonomic studies indicated that the culture is a new species and therefore has been designated Actinoplanes arizonaensis sp. nov. Two members of the complex, arizonins A1 and B1, exhibit moderate to potent in vitro antimicrobial activity against pathogenic strains of Gram-positive bacteria.     

Azinomycins A and B, new antitumor antibiotics. I. Producing organism, fermentation, isolation, and characterization

A strain of Streptomyces griseofuscus S42227 (FERM P-8443) was found to produce new antitumor antibiotics, called azinomycins A and B. The molecular formulas of azinomycins A and B were determined as C30H33N3O10 and C31H33N3O11, respectively. They were active against Gram-positive bacteria, Gram-negative bacteria and L5178Y cells in tissue culture.     

Tiacumicins, a novel complex of 18-membered macrolide antibiotics. I. Taxonomy, fermentation and antibacterial activity

A complex of 18-membered macrolide antibiotics has been discovered in the fermentation broth of strain AB718C-41. The producing culture, isolated from a soil sample collected in Hamden, Connecticut, was identified as a strain of Dactylosporangium aurantiacum and was designated D. aurantiacum subsp. hamdenesis subsp. nov. The antibiotic complex was produced in a New Brunswick 150-liter fermentor using a medium consisting of glucose, soybean oil, soybean flour, beef extract and inorganic salts. Several of the antibiotics were active against sensitive and multiple antibiotic-resistant strains of pathogenic Gram-positive bacteria.