A novel antibiotic, DC-86-M was isolated from the culture broth of a new isolate, DO-86, from the soil sample collected in Machida-shi, Japan. The producing organism was found to belong to Streptomycetes, for it formed aerial mycelia and chains of spores and its cell wall analyses revealed the presence of LL-diaminopimelic acid. The morphological, cultural and physiological characteristics of the strain DO-86 resemble closely those of Streptomyces luteogriseus and we concluded that the strain DO-86 could be designated as Streptomyces luteogriseus DO-86. The antibiotic was produced in the fermentation medium consisting of lactose 20 g, glucose 10 g, Pharmamedia 15 g, yeast extract 5 g, meat extract 10 g and CaCO₃ 2 g per liter of tap water.

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A novel antibiotic, DC-86-M was isolated from the culture broth of Streptomyces luteogriseus DO-86. The antibiotic has the molecular formula of C₁₇H₁₄N₂O₅ and belongs to the phenazine antibiotics. Its structure has been elucidated by mass and NMR spectra. It is active against Gram-positive and Gram-negative bacteria and experimental murine sarcoma 180.

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Two new macrolides, patulolide B and patulolide C, were isolated from a culture filtrate of Penicillium urticae S11R59 mutant. The structures of these macrolides were determined and their biological activities were investigated. These structures and biological activities were also compared with those of patulolide A which was produced by the same organism.

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The structure of mycosubtilin, a peptidolipid antibiotic from Bacillus subtilis, was revised by FAB mass spectrometry, 2D NMR spectrometry and also by Edman degradation of the peptide resulting from the N-bromosuccinimide reaction. Four homologous β-amino acid components were identified by capillary gas chromatography. The cyclopeptide mycosubtilin consists of seven α-amino acids in an LDDLLDL sequence closed by a β-amino acid linkage similar to that found in other antibiotics of the iturin group.

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Biosynthetic feeding experiments with ¹⁴C and ¹³C-labeled precursors in Kibdelosporangium aridum have established the biosynthetic origins of the heptapeptide aglycone of the aridicin antibiotics, and the tentative sequence of the later stage biosynthetic transformations. The aglycone moiety has been found to be derived from tyrosine, sodium acetate and L-methionine. It is suggested that the preformed aglycone is first mannosylated and then followed by the attachment of the glycolipid. The sugar oxidation to the glucuronic acid level was found to take place as a terminal step of the biosynthesis.

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In connection with the biosynthetic studies of the aridicin antibiotics in Kibdelosporangium aridum, various microorganisms, known to produce related glycopeptide antibiotics, have been examined for their glycosylating activity. A number of strains were found to mannosylate the aridicin aglycone, while Actinoplanes teichomyceticus was found to have deacylating activity as well. A protoplast system of K. aridum was developed and was found to possess novel glycosylating activity in addition to the mannosylating activity which was also present in the whole cells. Effects on the glycosylating activity by various membrane solubilizing agents have been discussed.

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Roxithromycin, formerly known as RU 28965 (9-[O[(2-methoxyethoxy)methyl]oxime]-erythromycin), is a novel 14 atom-membered semisynthetic macrolide with an antibacterial spectrum directed towards Gram-positive cocci and bacilli, Gram-negative cocci and some Parvobacteriaceae. The in vitro antibacterial activity of roxithromycin was compared with those of erythromycin and spiramycin against 275 clinical isolates by using 2-fold broth macro-dilution tests. The antibacterial spectrum of roxithromycin and erythromycin were qualitatively comparable (including the bacteriostatic type of activity and the profile of resistance), but minimal inhibitory concentrations of erythromycin were generally one half those of roxithromycin, except for Corynebacterium sp. and Bacteroides fragilis against which the new macrolide was more active. On the other hand, roxithromycin exhibited a superior in vivo antibacterial activity in laboratory animals, being up to six times more potent than erythromycin in curing experimentally infected mice. Roxithromycin showed high blood levels and long half-lives of elimination in rodents after oral administration, and its bioavailability amounted to 72% in mice and 85% in rats, compared to less than 10% for erythromycin. Roxithromycin was widely distributed throughout the body with a high degree of penetration into all tissues, particularly in the lungs.

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The 2-aminothiazol-4-yl-2-alkoxyiminoacetamido substituent-containing β-lactam antibiotics (cephalosporins and monobactams) develop a stable, concentration-dependent purple or cherry-red color after reaction with sodium nitrite in acidic condition. The color-formation is highly specific; it requires certain defined structural features such as the simultaneous presence of the intact aminothiazole-ring and an alkoxyimino substituent in the syn configuration. Other substituents on the β-lactam nucleus have effect only on the intensity of the color. This simple and fast colorimetric procedure was found to be useful not only for the detection of this class of β-lactam antibiotics but also for their quantitative spectrophotometric determination (λ_max 500 nm). A linear relationship exists between the intensity of the color plotted on a logarithmic scale and the concentration (12.5-200 μg/ml) of the compounds on an arithmetic scale. The β-lactams studied in this class with definitely positive purple-red color reaction are; cefotaxime, ceftizoxime, ceftazidime, ceftriaxone, cefmenoxime, cefodizime, ceftiolene, cefpirome, aztreonam, HR 109, FK 027 (cefixime), FR 19346, SK&F 88070, FR 13300, carumonam, YM 13115, BMY 28142, DN 9550, deacetylcefotaxime, deacetoxycefotaxime and deacetylcefotaxime lactone.

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Ascofuranone (AF) elevated natural cytotoxic activity of spleen when it was administered intraperitoneally to male mice. The elevation was observed both in low and high responder mice. AF-activated splenocytes lysed NK-resistant tumor cells, FM3A, P388 and sarcoma 180 cells as well as NK-sensitive YAC-1 cells. However, AF suppressed other lymphatic functions such as mitogenic responses and interleukin 2 production. Because AF did not activate splenic NK activity in vitro, the activation is assumed to be caused by a host-mediated process. One of the possibilities is modulation of the lipid metabolism of splenocytes. Thus, we examined splenic lipid contents and revealed that AF decreased splenic triglycerides without affecting other lipids. In contrast, the antibiotic significantly increased triglyceride in muscle.

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Nucleoticidin and melanocidins A and B exhibited potent inhibitory activity against 5'-nucleotidases from rat liver membrane and snake venom. Nucleoticidin retarded growth of Sarcoma 180 solid tumor, and melanocidins A and B prolonged the survival period of mice bearing B16 melanoma. These inhibitors enhanced phagocytic activity, interleukin-1 production and superoxide-generating activity of murine peritoneal macrophages. The tumor necrosis factor was also induced by the inhibitors. These results suggested that 5'-nucleotidase inhibitors inhibit tumor growth by modification of the immune system.

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The streptothricin-resistance gene of Streptomyces lavendulae No. 1080 was cloned in S. lividans using pIJ41 as a vector. From succloning experiments, the 1.6 kb BamH I fragment was determined to encode the structural gene. The cell extracts of S. lividans carrying the gene on the plasmid pKS7 had activity of inactivate streptothricin in the presence of S-acetyl coenzyme A, indicating that the gene product was streptothricin acetyltransferase.

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A plasmid was found in Nocardia orientalis (formerly Streptonryces orientalis). Physical characterization of the plasmid DNA indicates a size of 33.5 kb and a single cleavage site for EcoR I. The presence of plasmid, and variation in its copy member, did not directly affect vancomycin resistance or production levels. The plasmid represents the first to be isolated and characterized from a glycopeptide-producing nocardia.

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The pharmacokinetics of each drug on the concomitant administration of piperacillin (PIPC) and cefazolin (CEZ) or cefoperazone (CPZ) were studied in rabbits. When rabbits received the consecutive drip infusion administration of CEZ (0.71 mg/kg/minute) and PIPC (1.38 mg/kg/minute) and likewise of CPZ (0.72 mg/kg/minute) and PIPC (1.54 mg/kg/minute) for 1 hour, respectively, the serum half-lives of CEZ and CPZ were respectively prolonged about 1.8 and 1.6 times during drip infusion of PIPC than administered alone. However, when the sequence of administration were reversed, the serum levels of PIPC were not affected by the consecutive drip infusion administration of CEZ and CPZ. To study these findings in detail, the single intravenous dose of 20 mg/kg of CEZ and CPZ were administered under drip infusion of PIPC (2.65-2.93 mg/kg/minute). The serum half-lives of CEZ and CPZ were also prolonged about 5.4 and 1.9 times, respectively, whereas urinary excretion of CEZ, and urinary and biliary excretion of CPZ were reduced by PIPC. Moreover, when the single intravenous dose of 20 mg/kg of PIPC were administered under drip infusion administration of CEZ (0.96- 2.60 mg/kg/minute), the pharmacokinetics of PIPC was not affected by the presence of CEZ. However, under drip infusion administration of CPZ (2.60-2.70 mg/kg/minute), the PIPC serum half-life was prolonged about 1.4 times, and biliary excretion of PIPC was reduced but urinary excretion was not. From the results of renal clearance experiments, tubular secretion appeared to be the predominant mechanism of renal elimination for these three drugs. These results indicate that PIPC influences the pharmacokinetics of both drugs by the competitively inhibiting tubular secretion in CEZ, and tubular secretion and hepatic transport system in CPZ. Therefore, in this respect PIPC seems to have probenecid-like action.

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