A taxonomic study of Streptomyces strain T-36496, which produces an antibiotic effective against rice blast, revealed that it represented a new taxon and it was named Streptomyces novoguineensis sp. nov. The antibiotic, which was named amipurimycin, showed antifungal activity in vitro and considerable curative effect on leaf blast both in green house and field tests at concentrations ranging from 10 to 20 ppm. It was also effective against neck and panicle blast at the same concentration range.
A new antibiotic amipurimycin, active against Pyricularia oryzae in vitro and in vivo, was isolated from the culture filtrate of Streptomyces novoguineensis nov. sp. The antibiotic was purified by a combination of ion-exchange and adsorption chromatography based on its amphoteric water-soluble characteristics. Its molecular formula was estimated to be C20H27-31N7O8.H2O. Characteristic maxima in the UV spectrum and signals in the PMR and CMR spectra were similar to those of 2-aminopurine 9-(β-D)-riboside. These findings indicated that amipurimycin is a new nucleoside antibiotic and the first example of a natural product containing 2-amino-purine.
A soil isolate named Streptomyces hofunensis sp. nov. was found to produce seldomycin factors 1, 2, 3 and 5, new aminoglycoside antibiotics. Taxonomy of the producing organism, a study of cultural conditions for seldomycin production, and antibacterial activity of seldomycins are reported. Seldomycin factor 5 was the most active both in vitro and in vivo against gram-positive and negative bacteria.
An antibiotic complex consisting of four components, seldomycin factors 1, 2, 3 and 5 was isolated from the fermentation broth ofStreptomyces hofunensis sp. nov. by use of a cationic exchange resin. After silica gel column chromatography, the purified components were characterized as new aminoglycoside antibiotics by their physicochemical, chromatographic and antimicrobial properties.
The structures of seldomycin factors 1 and 2 have been determined by consideration of chemical degradation and spectral properties. Factor 1, also known as XK-88-1, is shown to be 6-0-(2-amino-2-deoxy-α-D-xylopyranosyl) paromamine (1) and factor 2, also known as XK-88-2, is shown to be 4'-deoxy-neamine (2GS). Mass spectral evidence has been obtained that suggests the most probable structure for seldomycin factor 3, also known as XK-88-3, is 6'-amino-6'-deoxyseldomycin factor 1 (12).
Microorganisms reduced the side-chain carbonyl of daunorubicin to yield 13-dihydrodaunorubicin (daunorubicinol; daunomycinol). This microbial transformation occurred under aerobic conditions in agitated baffled shake flasks incubated at 37°C. The microorganisms were first grown in a medium which supported dense growth. Daunorubicin-HCl was then added. Following a period of incubation, broths were adjusted to pH 10.0 and extracted with chloroform. Daunorubicinol was recovered and purified from the chloroform extracts by preparative TLC. Identity of the daunorubicinol was established by TLC and spectroscopy (UV-vis, IR, NMR, MS, CD and ORD). N-Acetyldaunorubicin was likewise reduced microbially to N-acetyldaunorubicinol. N-Acetyldaunorubicinol appears to be a new compound which is yet to be tested for antitumor activity.
Several derivatives of 5-ketocoriolin B (8, 11, 12) chemically modified at C-8 have been synthesized. These derivatives showed antitumor and antibacterial activity of the same degree as 5-ketocoriolin B (4) and diketocoriolin B (5) which were the most active members of the known coriolin group antibiotics. These derivatives were more stable than 4 and 5 in acidic or alkaline solution.
Two new penicillins and a new cephalosporin have been synthesized by condensing 2-hydroxy-l-naphthaldehyde with epicillin, 6-aminopenicillanic acid and cephradine, and subsequently reducing the SCHIFF bases with NaBH4. The antimicrobial activities of these compounds are also described.
The first synthesis of 6'-C-aminomethyl derivatives (6'-epimers) of 3'-deoxyparomamine is reported starting from 3'-deoxyparomamine by way of 6'-O-tritylation, O-acetylation, hydrolysis of the trityl group, conversion of the 6'-hydroxyl group into an aldehyde group, nitromethane condensation of the aldehyde group and catalytic reduction of the nitro group into an amino group.
Chloramphenicol-3-acetate esterase activity was detected in cell-free extracts of strains of Streptomyces venezuelae, Streptomyces sp. and Streplosporangium viridogriseum var. kofuense which produced chloramphenico] and also Corynebacterium hydrocarboclsastus which produced chloramphenicol analogs (corynecins). None of the cell-free extracts of chloramphenicol- or corynecin-producing strains possessed chloramphenicol acetyltransferase activity under conditions which avoided the influence of the esterase activity. Among 20 strains examined that did not produce chloramphenicol, chloramphenicol acetyltransferase was detected in cell-free extracts of one strain of Streptomyces coelicolor Müller and one strain of S. fradiaeNS ISP5063.
Previously described cases of streptomycin inactivation by R-factor carrying strains of E. coli have not lead to any measurable decrease in antimicrobial potency in the bulk substrate toward the culture. In these cases each cell inactivates only a few molecules. Out of 1, 800 strains of E. coli we have isolated five strains which inactivate streptomycin in large amounts giving a final concentration of the inactivation product of 0.25 mg/ml in 36 hours. Unlike all other streptomycin-resistant strains investigated these five strains were sensitive to butyl-streptomycylamine, a streptomycin derivative acting in the same way as streptomycin. The crude inactivation product has been isolated. Inorganic phosphate is liberated by treatment with alkaline phosphatase resulting in a streptomycin-like compound without any antimicrobial activity.
By mutation and strain improvement techniques idiotrophs of Micromonospora purpurea, the gentamicin-producing organism, were obtained which require an exogenous source of 2-deoxystreptamine in order to produce gentamicin. Streptamine incorporation afforded a mixture of 2-hydroxygentamicin C as a complex of essentially the C1 and C2 components whereas 2-deoxystreptamine when incorporated by the same idiotroph afforded the same mixture of C1, C2 and C1a gentamicins as the parent (m1) organism. The 2-hydroxygentamicin C complex exhibited broad-spectrum antibiotic activity with an in vitro potency less than that for the gentamicin C complex, but with greater activity against selected gentamicin C resistant organisms. The LD50 (i.v.) in mice of the 2-hydroxygentamicin C complex indicated that it had approximately half the toxicity of the gentamicin C complex. 2, 5-Dideoxystreptamine afforded a C1, C2, and C1a mixture of 5-deoxygentamicins, which also had broad spectrum activity, and exhibited improved activity against several gentamicin-acetylating strains of resistant bacteria. The LD50 (i.v.) in mice of the 5-deoxygentamicin C complex indicated that it was about 2.5 times more toxic than the gentamicin C complex. Two derivatives of 2, 5-dideoxystreptamine afforded the same mixture of 5-deoxygen-tamicins. 2-Epistreptamine upon supplementation to a broth containing growing cultures of these idiotrophs also produced antibiotic.
A mutant of Micromonospora purpurea, which produces the gentamicin complex only when 2-deoxystreptamine is added to the fermentation medium, produces a new antibiotic complex, 2-hydroxygentamicin, when streptamine or 2, 4, 6/3, 5-pentahydroxycyclohexanone is added to the fermentation medium. This mutant also produces the gentamicin complex when 2, 4/3, 5-tetrahydroxycyclohexanone is added to the fermentation medium. The C1 and C2 components of 2-hydroxygentamicin have broad spectrum in vitro antibacterial activity similar to the gentamicin C1 and C2 components, but with greater activity against some gentamicin-resistant strains.
The incorporation of uniformly 14C-labeled compounds into the streptothricin-type antibiotic nourseothricin was studied with a strain of Streptomyces noursei JA 3890b. 6.5% of radioactivity from U-14C-L-arginine was incorporated into the antibiotic, while glutamic acid, aspartic acid, alanine, proline, glycine and leucine displayed much lower incorporations. Furthermore, 95% of the activity incorporated from arginine was located in the streptolidine moiety supporting the suggestion that this subunit of streptothricin antibiotics is formed via the dehydroarginine pathway.
A gene coding for desensitized L-threonine dehydratase was transduced with phage PS20 into a leucine accumulator of Serratia marcescens Sr41. The transductant converted L-threonine to α-ketobutyrate, a precursor of both norvaline and isoleucine. An isoleucine-valine auxotroph of the transductant accumulated large amount of norvaline from L-threonine as well as from D-threonine.
Amphotericin B methyl ester (AME), the chemically modified derivative of amphotericin B, induced a concentration-dependent growth stimulatory effect on B82 mouse cells as indicated by increased 24- and 72-hour viable cell number, growth rate and DNA and RNA synthesis. In contrast, AME was not growth promoting toward RAG mouse cells or B82-RAG somatic cell hybrids, while hybrid cells exhibited the increased AME resistance pattern of B82 parental cells. A dissociation between the phenotypic expression of growth stimulation and polyene sensitivity was demonstrated in intraspecific mouse hybrids.