Lomofungin,a New Antibiotic Produced by Streptomyces lomondensis sp. n

Lomofungin is a new antimicrobial agent obtained from the culture broth of Streptomyces lomondensis sp. n. UC-5022. Lomofungin is an acidic, olive-yellow, crystalline compound which inhibits, in vitro, a variety of pathogenic fungi, yeasts, and gram-positive and gram-negative bacteria.     

2070-DTI,A Topoisomerase Inhibitor Produced by Streptomyces sp. Strain No. 2070

A novel inhibitor of topoisomerase II designated as 2070-DTI was isolated from the culture filtrate of Streptomyces sp. strain No. 2070. The structure was determined to be that of the known soyasaponin I on the basis of spectroscopic methods (NMR and MS). 2070-DTI strongly inhibited the decatenation activity of human placenta topoisomerase II in a noncompetitive manner, and weakly inhibited or was inert towards the relaxation activities of various topoisomerase I's and DNA-related enzymes. 2070-DTI is an inhibitor belonging to the cleavable complex-nonforming type without DNA intercalation.     

An Inhibitor of S-Hemolysin,SHI, Produced by Streptomyces sp. Strain No. 6288

Streptomyces sp. strain No. 6288 produces S-Hemolysin, which is a unique phospholipase C with a high substrate specificity for sphingomyelin. Moreover, the strain also produced two kinds of phospholipase inhibitors, designated as SHI and S-PLI, in different phases of cultivation. The purified SHI was shown to be a basic substance containing an amino group and glycoside moiety, and it was a more effective inhibitor of S-Hemolysin and sphingomyelinase from Streptomyces sp. with a higher substrate specificity for sphingomyelin than α-toxin from Clostridium perfringens.     

Cell Aggregation Factor Produced by Streptomyces sp. Strain No. A-3315

We searched for a new aggregation factor, and found one we named 3315-AF in the culture filtrate of Streptomyces sp. strain No. A-3315. 3315-AF was purified by active carbon treatment, ethanol precipitation, gel filtration on Sepharose 2B, ether extraction, silica gel chromatography and gel filtration on Sephadex LH-20. 3315-AF was found to be a triglyceride which consists of myristic acid, pentadecanoic acid, and palmitic acid. The aggregation activity of 3315-AF was maximum around pH 8.0 at 30°C and the activity increased by addition of metallic ions such as calcium and cobalt. Hyaluronic acid, ovalbumin, BSA, and casein inhibited the aggregation activity. 3315-AF aggregated Proteus vulgaris and HeLa cells as well as Serratia marcescens and weakly aggregated Saccharomyces cerevisiae, Candida albicans, C. neoformans, and Leukemia P388, but it was inert to human erythrocytes and Sarcoma 180.     

Some Properties of Amylase Inhibitor Produced by Streptomyces sp. No. 280

A strain of Streptomyces produces a new substance capable of inactivating some amylases. This has not been reported by previous workers.

This amylase inhibitor was purified by means of acetone treatment, active carbon adsorption and column chromatography on DEAE-cellulose.

It was dialyzable through a cellophane membrane and soluble in water and methyl alcohol. The inhibitor had a small molecular weight and was a peptide-like substance. The inhibiting substance was resistant to the temperatures, and acted as inhibitor of glucoamylase, bacterial saccharogenic α-amylase, salivary and pancreatic α-amylases.     

Isolation and Structure Elucidation of a New Antifungal and Antibacterial Antibiotic Produced by Streptomyces sp. 201

An antibacterial and antifungal antibiotic was isolated from the culture filtrate of Streptomyces sp. 201, and its structure was determined as 2-methyl-heptyl isonicotinate by extensive use of NMR spectroscopy. The compound exhibited marked antimicrobial activity against Bacillus subtilis, Shigella sp., Klebsiella sp., E. coli, Proteus mirabilis, and the pathogenic fungi, Fusarium moniliforme, F. semitectum, F. oxysporum, F. solani and Rhizoctonia solani.     

Promoinducin,a Novel Thiopeptide Produced by Streptomyces sp. SF2741

Our continued screening to find tipA promoter-inducing substances resulted in the isolation of promoinducin from a mycelial extract of Streptomyces sp. SF2741. Based on various 1D- and 2D-NMR studies, including field gradient (FG)-COSY, HSQC, FG-HMBC, phase-sensitive ¹³C-decoupled HMBC and NOESY experiments, promoinducin’s structure was established to be a thiopeptide composed of threonine, some unusual amino acids masked at their carboxyl groups by thiazole or methyloxazole rings, sulfomycinamate and five dehydroalanine residues. Promoinducin induced the tipA promoter at 40 ng/ml, and also exhibited strong antibacterial activity against some Gram-positive bacteria.     

Kalafungin, a New Antibiotic Produced by Streptomyces tanashiensis Strain Kala

Kalafungin is a new antimicrobial agent obtained from the culture broth of a soil isolate of Streptomyces tanashiensis, designated Streptomyces tanashiensis strain Kala UC-5063. Kalafungin is a chemically stable, nonpolyene agent which is ex-extremely inhibitory in vitro against a variety of pathogenic fungi, yeasts, protozoa, gram-positive bacteria, and, to a lesser extent, gram-negative bacteria.     

Scopafungin, a Crystalline Antibiotic Produced by Streptomyces hygroscopicus var. enhygrus var. nova

Scopafungin (U-29,479) is a crystalline, nonpolyenic antimicrobial agent obtained from the culture broth of Streptomyces hygroscopicus var. enhygrus var. nova UC-2397. Scopafungin inhibits, in vitro, a variety of pathogenic fungi, yeasts, and gram-positive bacteria.     

Purification and Properties of Lipase Activator Produced by Streptomyces sp. Strain No. BR-1381

To obtain actinomycetes capable of producing new enzyme affectors such as enzyme inhibitors or activators, a screening test was carried out. Streptomyces sp. strain No. BR-1381 isolated in our laboratory produced a proteinous lipase activator abbreviated as LAV. LAV was purified from the culture filtrate by salting-out with ammonium sulfate, DEAE-cellulose column chromatography and gel filtration on Sephadex G-100. LAV was stable in the pH range from 3 to 7 at 37°c for 20 hr and in a wider range of pH at 4°C for 5 days. LAV itself was very stable against heat treatment, but LAV did not have any effect on the thermal stability of Phycomyces nitens lipase. LAV activated several microbial lipases, but did not activate pancreatic or rice bran lipases. LAV particularly showed strong activation for Phycomyces nitens lipase.     

Streptomyces multispiralis nov. sp. and a New Antibiotic,Neohumidin

A streptomycete isolated in our laboratories was found to produce a new antibiotic effective for the control of sheath blight of the rice plant. As a result of taxonomical study it was proved to belong to a new species and therefore it was named Streptomyces multispiralis nov. sp. From its fermented broth, the antibiotic was isolated and crystallized from benzene. After the comparison of its physicochemical and biological properties with those of known antibiotics, it was considered to be a new antibiotic and named neohumidin. It inhibited the growth of certain phytopathogenic fungi, saprophytic fungi, yeasts and gram-positive bacteria.     

Durhamycin, a Pentaene Antifungal Antibiotic from Streptomyces durhamensis sp. n

Durhamycin, derived from a previously undescribed soil isolate, is an apparently new antibiotic active against many of the fungi pathogenic for man and animals. Cultural and morphological characteristics and biochemical reactions of Streptomyces durhamensis are detailed. Methods of extraction of the antibiotic, physicochemical properties, antimicrobial spectrum, and results of mouse toxicity and protection tests are given.     

Further Purification of Amylase Inhibitor Produced by Streptomyces sp.

The amylase inhibitor produced by Streptomyces sp. consisted of, at least, three kinds of inhibiting materials (inhibitor A, B and C). These inhibitors were separated by the Chromatographic techniques on Amberlite CG–120 and Dowex 1 × 2, and by paper chromatography etc.

Inhibitor A, B and C seemed to contain both carbohydrates and amino acids, but the specific activities (I. U./mg glucose) of the inhibitors A, B and C were different, that is, 18,800, 45,700 and 59,000, respectively. Also their ratios of amino acids to neutral sugars (expressed by moles of leucine per those of glucose) were approximately 0.09 (inhibitor A), 2.77 (inhibitor B) and 0.58 (inhibitor C).     

Two New Butenolides Produced by an Actinomycete Streptomyces sp.

Two new butenolides, (4S)‐4,10‐dihydroxydodec‐2‐en‐1,4‐olide ( 1 ) and (4S)‐4,8,10‐trihydroxy‐10‐methyldodec‐2‐en‐1,4‐olide ( 2 ), together with three known compounds, MKN‐003B ( 3 ), MKN‐003C ( 4 ), and cyclo(Ala‐Leu) ( 5 ), were isolated from the culture broth of a bacterium of the genus Streptomyces derived from soil environment. The structures of these compounds were elucidated on the basis of spectroscopic analysis. The inhibitory activities of the butenolides against eight pathogenic fungi were evaluated. All of the butenolides showed moderate‐or‐weak antifungal activities in a broth microdilution assay.     

2070-DTI, a topoisomerase inhibitor produced by Streptomyces sp. strain No. 2070

A novel inhibitor of topoisomerase II designated as 2070-DTI was isolated from the culture filtrate of Streptomyces sp. strain No. 2070. The structure was determined to be that of the known soyasaponin I on the basis of spectroscopic methods (NMR and MS). 2070-DTI strongly inhibited the decatenation activity of human placenta topoisomerase II in a noncompetitive manner, and weakly inhibited or was inert towards the relaxation activities of various topoisomerase I's and DNA-related enzymes. 2070-DTI is an inhibitor belonging to the cleavable complex-nonforming type without DNA intercalation.     

Induction of Antibiotic Formation in Streptomyces sp. No. 362 by the Change of Cellular Fatty Acid Spectrum

Microorganisms which require oleic acid for the formation of antibiotics were screened. Streptomyces sp. No. 362, one of the selected organisms, produced antimicrobial substances only when oleic acid, palmitic acid or the high concentration of l-glutamic acid (or l-glutamine) was supplemented to the medium. The cellular fatty acid composition was changed by the supplement of these fatty acids, but not by l-glutamic acid (or l-glutamine). Antibiotic-producing cells had about 4 to 10 times larger amino acid pools, especially l-glutamic acid pool, and hexosamine pools. The ability for l-glutamate uptake of cells grown in the oleic or palmitic acid supplemented medium was markedly enhanced and the efflux of the accumulated l-glutamate was reduced. The antibiotic produced by this strain was identified as one of the streptothricin-group antibiotics and the role of these additives in the antibiotic formation is discussed.     

Human Erythrocyte Receptor of l-Fucose-specific Lectin Produced by Streptomyces sp.

L-Fucose-specific lectin produced by Streptomyces no. 16-3 (SFL 16-3) was labeled with N- succinimidyl-[2, 3-³H]-propionate to quantitatively investigate its binding to human erythrocytes. The binding inhibition by sugars was competitive, and 5mM L-fucose or 20 mM d-mannose completely inhibited the binding. Among plant lectins, Lotus tetragonolobus, Ulex europeus I, soybean and wheat germ lectin showed competitive inhibition. The association constant and the average number of binding sites for human blood group O erythrocytes were approximately 3 × 10⁷ M^-1 and 1 × 10⁶ cell^-1, respectively. Trypsinization of erythrocytes preferentially increased the number of binding sites for human A and B erythrocytes but not for O erythrocytes.

Membrane components were extracted from human B and O erythrocytes and their binding activity for SFL 16-3 was tested using the hemagglutination-inhibition assay. Poly(glycosyl)-ceramide was the predominant receptor and its fucosyl residue was essential for binding. The crude glycoprotein fraction showed only slight inhibition activity.