ABSTRACT
Strain C39217-R109-7 (ATCC 53791) is an actinomycete strain isolated from a soil sample collected at Puerto Viejo, Peru. It produces a new antitumor antibiotic, designated pyrrolosporin A. Taxonomic studies on its morphological, cultural and physiological characteristics identified this producing strain as Micromonospora sp. C39217-R109-7. Pyrrolosporin A shows antimicrobial activity against Gram-positive bacteria and it is weakly active against Gram-negative bacteria. Pyrrolosporin A prolongs the life span of mice inoculated with P388 leukemia cells.
Subject(s)
Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Antibiotics, Antineoplastic/metabolism , Antibiotics, Antineoplastic/pharmacology , Fermentation/physiology , Macrolides , Micromonospora/metabolism , Animals , Dose-Response Relationship, Drug , Industrial Microbiology/methods , Leukemia/drug therapy , Mice , Mice, Inbred Strains , Microbial Sensitivity Tests , Micromonospora/classificationABSTRACT
A fungal metabolite, BMS-182123, which inhibited bacterial endotoxin-induced production of tumor necrosis factor (TNF-alpha) in murine macrophages and human peripheral blood monocytes (in vitro), was isolated from the culture broth of Penicillium chrysogenum strain V39673. The effective BMS-182123 concentration (IC50) resulting in 50% inhibition of lipopolysaccharide-induced TNF-alpha production in murine macrophages and human monocytes was 600 ng/ml and 4.0 microgram/ml, respectively. BMS-182123 suppressed the lipopolysaccharide-induced TNF-alpha promoter activity and did not affect the stability of posttranscriptional mRNA. Addition of hydrophobic resin, Amberlite XAD-8 (1%), to the fermentation enhanced the production of BMS-182123 by 5.5 fold. A total of 577 mg pure BMS-182123 was recovered from a 250-liter fermentation supplemented with 1% Amberlite XAD-8.
Subject(s)
Bridged-Ring Compounds/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Monocytes/drug effects , Monocytes/metabolism , Penicillium/metabolism , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/biosynthesis , Animals , Base Sequence , Bridged-Ring Compounds/chemistry , Bridged-Ring Compounds/metabolism , DNA Probes/genetics , Fermentation , Humans , In Vitro Techniques , Lipopolysaccharides/pharmacology , Mice , Molecular Sequence Data , Molecular Structure , Penicillium/classification , Promoter Regions, Genetic/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , Tumor Necrosis Factor-alpha/geneticsABSTRACT
Micromonospora sp C39500, isolated in our laboratory from a soil sample, produced a complex of seven novel depsipeptide antitumor antibiotics, designated korkormicins. The major component of the complex, korkormicin A, has a MW of 1452 and a molecular formula of C66H84N16O22. Korkormicin A exhibits potent in vivo antitumor activity against P388 leukemia and M109 lung carcinoma implanted intraperitoneally (ip) in mice, with effective doses of 0.05-0.20 mg kg-1 injection-1, for five or three ip injections, respectively. It is also active against Gram-positive bacteria but inactive against Gram-negative bacteria. The production of korkormicin A was enhanced by 3-fold when 0.1% L-valine was added to the production culture at 48 h. A titer of 401.0 micrograms ml-1 was achieved in the fermenter culture supplemented with 0.1% L-valine.
Subject(s)
Antibiotics, Antineoplastic/biosynthesis , Micromonospora/metabolism , Animals , Antibiotics, Antineoplastic/pharmacology , Carcinoma/drug therapy , Culture Media/chemistry , Drug Screening Assays, Antitumor , Female , Fermentation/drug effects , Fermentation/physiology , Leukemia P388/drug therapy , Lung Neoplasms/drug therapy , Mice , Mice, Inbred BALB C , Mice, Inbred DBA , Micromonospora/classification , Micromonospora/drug effects , Molecular Weight , Neoplasm Transplantation , Nitrogen/pharmacology , Valine/pharmacologyABSTRACT
Strain L585-6 (ATCC 53650) is an actinomycete isolated from a soil sample collected in Maharastra State, India. It produces a new chromoprotein antitumor antibiotic, designated kedarcidin. Taxonomic studies demonstrated that strain L585-6 is an unidentified and unknown actinomycete. Kedarcidin shows potent antitumor activity against implanted P388 leukemia (3.3 micrograms/ml/kg) and B16 melanoma (2 micrograms/kg) in mice. Kedarcidin also shows potent antimicrobial activity against Gram-positive bacteria but no activity against Gram-negative bacteria.
Subject(s)
Actinomycetales/metabolism , Anti-Bacterial Agents , Antibiotics, Antineoplastic/biosynthesis , Peptides , Actinomycetales/analysis , Animals , Antibiotics, Antineoplastic/pharmacology , Fermentation , Intercellular Signaling Peptides and Proteins , Leukemia P388/drug therapy , Melanoma, Experimental/drug therapy , Mice , Mice, Inbred Strains , Protein Biosynthesis , Proteins/pharmacologyABSTRACT
Strain C39108-P210-51 (ATCC 53653), an actinomycete isolated from a soil sample collected in India, was found to produce a new antitumor antibiotic, designated himastatin. Taxonomic studies on its morphological, cultural and physiological characteristics identified this producing strain as Streptomyces hygroscopicus C39108-P210-51. Himastatin shows antimicrobial activity against Gram-positive bacteria but it is inactive against Gram-negative bacteria. Himastatin prolongs the life span of mice inoculated with P388 leukemia and B16 melanoma cells.
