Dethymicin, a novel immunosuppressant isolated from an Amycolatopsis. Fermentation, isolation, physico-chemical properties and biological activities.

In the course of screening for immunomodulators inhibiting the mixed lymphocyte culture reaction (MLCR), we found a novel immunosuppressant, dethymicin in mycelium of Amycolatopsis mediterranei MI710-51F6. From physico-chemical properties and biological activity it is different from immunosuppressants produced by microorganisms such as cyclosporins, FK506 and rapamycin. It inhibited immune responses in vitro and in vivo, and prolonged skin allograft in rats.     

FR901469, a novel antifungal antibiotic from an unidentified fungus No.11243. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological properties

FR901469 is a novel antifungal antibiotic produced by an unidentified fungus No.11243. This compound was isolated from the culture broth by solvent extraction, HP-20 and YMC ODS gel column chromatography, and lyophilization. FR901469 is a white powder which melts at 182 approximately 187 degrees C and possesses the molecular formula C71H116N14O23. This compound has good water solubility. FR901469 inhibited the activity of 1,3-beta-glucan synthase from Candida albicans with an IC50 value of 0.05 microg/ml, and displayed greater inhibitory activity than other 1,3-beta-glucan synthase inhibitors such as, WF11899A, echinocandin B, aculeacin A, and papulacandin B.     

Atpenins, new antifungal antibiotics produced by Penicillium sp. Production, isolation, physico-chemical and biological properties

Penicillium sp. FO-125, a soil isolate, was found to produce a new antifungal antibiotic complex named atpenin. Three components A4, A5 and B were isolated from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography and HPLC. The molecular formula of atpenins A4, A5 and B were determined to be C15H22NO5Cl, C15H21NO5Cl2 and C15H23NO5, respectively, on the basis of high resolution electron impact mass spectrometry and elemental analysis. They are active against filamentous fungi, especially, Trichophyton sp.     

TA-3037A, a new inhibitor of glutathione S-transferase, produced by actinomycetes. I. Production, isolation, physico-chemical properties and biological activities.

TA-3037A, a new inhibitor of glutathione S-transferase was discovered in the fermentation broth of Streptomyces sp. TA-3037. It was purified by chromatography followed by solvent extraction and then isolated as yellow needles. TA-3037A has the molecular formula of C16H11NO4. It was competitive with the substrate, and the inhibition constant (Ki) was 4.9 microM.     

Diperamycin, a new antimicrobial antibiotic produced by Streptomyces griseoaurantiacus MK393-AF2. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities

Antibacterial antibiotics, diperamycin (1) was produced in the culture broth of Streptomyces griseoaurantiacus MK393-AF2. Various spectroscopic analyses of 1 suggested that 1 belonged to a member of cyclic hexadepsipeptide antibiotic. Antibiotic 1 had potent inhibitory activity against various Gram-positive bacteria including Enterococcus seriolicida and methicillin-resistant Staphylococcus aureus.     

Luminamicin, a new antibiotic. Production, isolation and physico-chemical and biological properties

A new antibiotic, luminamicin, was isolated from the culture broth of an actinomycete strain OMR-59. It exhibits antibacterial activity against anaerobic bacteria, especially against Clostridium sp. The molecular formula of the antibiotic was determined as C32H38O12 on the basis of high resolution mass spectrum, elemental analysis and NMR spectrum.     

Nagstatin, a new inhibitor of N-acetyl-beta-D-glucosaminidase, produced by Streptomyces amakusaensis MG846-fF3. Taxonomy, production, isolation, physico-chemical properties and biological activities.

Nagstatin, a new inhibitor of N-acetyl-beta-D-glucosaminidase (NAG-ase) was discovered in the fermentation broth of Streptomyces amakusaensis MG846-fF3. It was purified by chromatography on Dowex 50W, Avicel and Sephadex LH-20 followed by the treatment of active carbon and then isolated as colorless powder. Nagstatin has the molecular formula of C12H17N3O6. It is competitive with the substrate, and the inhibition constant (Ki) was 1.7 x 10(-8) M.     

Herquline, a new alkaloid produced by Penicillium herquei. Fermentation, isolation and properties.

A new alkaloid named herquline has been isolated from culture broth of Penicillium herquei Fg-372 by solvent extraction and silica gel chromatography. The molecular formula of herquline has been determined as C19H26N2O2 on the basis of elemental analysis and its high resolution mass spectrometry. The compound does not possess antimicrobial activities, but weakly inhibits blood platelet aggregation induced by adenosine diphosphate.     

Diheteropeptin, a new substance with TGF-beta-like activity, produced by a fungus, Diheterospora chlamydosporia. I. Production, isolation and biological activities

A new metabolite, diheteropeptin, was found in the culture broth of Diheterospora chlamydosporia Q58044 by screening for TGF-beta-like active substances. Diheteropeptin was extracted from the culture supernatant and purified by a series of chromatographies such as silica gel, gel filtration and HPLC. Diheteropeptin exhibited cytostatic activity in Mv1Lu cells with an IC50 value of 20.3 microM and inhibited histone deacetylase.     

Decatromicins A and B, new antibiotics produced by Actinomadura sp. MK73-NF4. I. Taxonomy, isolation, physico-chemical properties and biological activities

New antibiotics designated decatromicins A and B were isolated from the culture broth of Actinomadura sp. MK73-NF4. They were purified by butyl acetate extraction, silica gel column chromatography, silica gel TLC and Sephadex LH-20 column chromatography. Decatromicins A and B inhibited growth of Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA).     

Further new milbemycin antibiotics from Streptomyces bingchenggensis. Fermentation, isolation, structural elucidation and biological activities

Three new alpha-class milbemycins from Streptomyces bingchenggensis, named milbemycins alpha28, alpha29 and alpha30, have been isolated and characterized. On the basis of detailed spectroscopic analysis and comparison with reported data, their structures were determined to be the 22alpha-hydroxy, 23beta-O-(2-methylbutanoyl) milbemycin alpha9, 22alpha-hydroxy, 23beta-O-(2,4-dimethylpentanoyl) milbemycin alpha9 and 22alpha-hydroxy, 23beta-O-(2-methylbutanoyl) milbemycin A4, respectively. Milbemycins alpha28 and alpha29 are the first reported milbemycins that possess both C-26 and C-23 substituents. These three new milbemycins possess potent acaricidal and nematocidal activity.     

Lactonamycin, a new antimicrobial antibiotic produced by Streptomyces rishiriensis MJ773-88K4. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

Lactonamycin (1) was isolated from a culture broth of Streptomyces rishiriensis MJ773-88K4. Antibiotic 1 exhibited antimicrobial activities against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE).     

Tyropeptins A and B, new proteasome inhibitors produced by Kitasatospora sp. MK993-dF2. I. Taxonomy, isolation, physico-chemical properties and biological activities

Tyropeptins A and B, new proteasome inhibitors, were isolated from the culture broth of Kitasatospora sp. MK993-dF2. They were purified using ethyl acetate extraction, silica gel column chromatography, Sephadex LH-20 column chromatography and HPLC. Tyropeptin A inhibited the chymotrypsin-like (ChT-L) and trypsin-like (T-L) activities of 20S proteasome with IC50 values of 0.1 microg/ml and 1.5 microg/ml respectively, but did not inhibit the peptidylglutamyl-peptide hydrolyzing (PGPH) activity of 20S proteasome at a concentration of 100 microg/ml. The inhibitory activities of tyropeptin A were about two times as strong as that of tyropeptin B. Taxonomy of the producing strain is also described.     

Cyclooctatin, a new inhibitor of lysophospholipase, produced by Streptomyces melanosporofaciens MI614-43F2. Taxonomy, production, isolation, physico-chemical properties and biological activities.

Cyclooctatin has been isolated from Streptomyces melanosporofaciens MI614-43F2 as part of a program designed to find microorganism-produced inhibitors of lysophospholipase. It was purified by chromatography on silica gel, Capcell Pak C18 (HPLC) and Sephadex LH-20 followed by solvent extraction and then isolated as a colorless powder. Cyclooctatin has the molecular formula of C20H34O3. It is competitive with the substrate, and the inhibition constant (Ki) was 4.8 x 10(-6) M.     

Studies on new antibiotics SF2415. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities

A new species of Streptomyces is described for which the name Streptomyces aculeolatus is proposed. The organism produces new antibiotics SF2415A1, A2, A3, B1, B2 and B3 active against Gram-positive bacteria. Empirical molecular formulae of the antibiotics SF2415A1, A2, A3, B1, B2 and B3 were determined to be C26H31N2O5Cl, C26H30N2O5, C26H30N2O5Cl2, C26H33O5Cl, C26H32O5 and C26H32O5Cl2, respectively.     

A new antimitotic substance, FR182877. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities

Using the characteristic morphological changes of mammalian cells, we screened novel antimitotic substances and found that a strain of Streptomyces sp. No.9885 produced FR182877. This substance was isolated from the culture broth by ethyl acetate extraction, silica gel column chromatography and ODS column chromatography. Structural studies on FR182877 suggested that it had a unique hexacyclic structure encompassing its highly strained double bond. FR182877 exhibited potent antitumor activities against murine ascitic tumor and solid tumor in vivo.     

PI-200 and PI-201, new platelet aggregation inhibitors produced by Streptomyces sp. A7498. Taxonomy, fermentation, isolation, physico-chemical properties, structure determination and biological properties.

Two new platelet aggregation inhibitors, PI-200 and PI-201 were isolated from the fermentation broth of Streptomyces sp. A7498. PI-200 and PI-201 inhibited ADP-induced aggregation of rabbit platelets with an IC50 of 3.8 x 10(-4) M and 7.1 x 10(-4) M, respectively.     

Mycoversilin, a new antifungal antibiotic. I. Fermentation, isolation and biological properties

A new antifungal antibiotic, mycoversilin, was isolated from the culture filtrate of Aspergillus versicolor (N5)17 by repeated column chromatography and recrystallized from ethyl acetate as homogeneous fine needles. Maximum production took place in a medium containing 4% glucose and 1% peptone at pH 3.5, temperature 28 degrees C after 8-9 days of incubation under stationary condition. Mycoversilin is a narrow spectrum antibiotic with activity against filamentous fungi, particularly Trichophyton rubrum (MIC 15 micrograms/ml).     

Kigamicins, novel antitumor antibiotics. I. Taxonomy, isolation, physico-chemical properties and biological activities

Novel antibiotics named kigamicin A, B, C, D, and E were discovered from the culture broth of Amycolatopsis sp. ML630-mF1 by their selective killing activity against PANC-1 cells only under a nutrient starved condition. Under a condition of nutrient starvation, kigamicins A, B, C, and D inhibited PANC-1 cell survival at 100 times lower concentration than in normal culture. Kigamicins showed antimicrobial activity against Gram-positive bacteria including methicillin resistant Staphylococcus aureus (MRSA). Kigamicin D inhibited the growth of various mouse tumor cell lines at IC50 of about 1 microg/ml.     

SQ 28,332, a new monobactam produced by a Flexibacter sp. Taxonomy, fermentation, isolation, structure determination and biological properties

A new monobactam SQ 28,332 has been isolated from fermentations of a Flexibacter sp. and the structure 3 was deduced from its spectroscopic properties. SQ 28,332 exhibits weak antibacterial activity.