Bacillaene, a novel inhibitor of procaryotic protein synthesis produced by Bacillus subtilis: production, taxonomy, isolation, physico-chemical characterization and biological activity.

Bacillaene, a novel polyene antibiotic, was discovered and isolated from fermentation broths of a strain of Bacillus subtilis. The novel antibiotic has a nominal molecular weight of 580 and an empirical formula of C35H48O7. Bacillaene is active against a broad spectrum of bacteria in agar-plate diffusion assays. Studies in vitro indicate that the antibiotic inhibits prokaryotic protein synthesis but not eukaryotic protein synthesis. Cell survival studies performed with strains of Escherichia coli indicate that the antibiotic is a bacteriostatic agent.

Dactylocyclines, novel tetracycline derivatives produced by a Dactylosporangium sp. I. Taxonomy, production, isolation and biological activity.

A screen for antibiotics with activity against tetracycline-resistant microorganisms has led to the isolation of Dactylosporangium sp. (ATCC 53693), a producer of several novel tetracycline derivatives. The major fermentation products, dactylocyclines A and B, were purified and MIC values determined against tetracycline-resistant and tetracycline-sensitive Gram-positive bacteria. The dactylocyclines represent the first naturally occurring tetracycline C2 amides which lack cross resistance with tetracycline.

SQ 30,957, a new antibiotic produced by Penicillium funiculosum. Taxonomy, fermentation, isolation, structure determination, synthesis and antibacterial activity.

A new antibiotic, SQ 30,957, 4-diazo-3-methoxy-2,5-cyclohexadien-1-one, has been isolated from fermentation broths of Penicillium funiculosum. The structure (1) was deduced from its spectroscopic properties and its degradation reaction. SQ 30,957 has excellent activity against anaerobic bacteria such as Clostridium and Bacteroides and has moderate activity against aerobic bacteria. The compound has an LD50 of less than 17 mg/kg in mice by intraperitoneal administration.

Two new inhibitors of phospholipase A2 produced by Penicillium chermesinum. Taxonomy, fermentation, isolation, structure determination and biological properties.

Plastatin and the known fungal metabolite, luteosporin, have been isolated from fermentations of Penicillium chermesinum as inhibitors of porcine pancreatic phospholipase A2 (PLA2). Structure 1 for plastatin was deduced from its spectroscopic properties. Plastatin and luteosporin inhibited pancreatic PLA2 competitively with Ki values of 0.89 microM and 12.8 microM, respectively. PLA2 preparations from Naja naja and Crotalus adamanteus were not significantly inhibited by plastatin and luteosporin.

Sulfur metabolism in the biosynthesis of monobactams.

We studied the biosynthesis of monobactams with respect to sulfur metabolism in Chromobacterium violaceum, Acetobacter sp., and Agrobacterium radiobacter. All three organisms used inorganic sulfur for monobactam production. When sulfur-containing amino acids were assayed as a source of sulfur for monobactam production, C. violaceum used cystine but not cysteine or methionine, Acetobacter sp. used all three compounds, and A. radiobacter used none. 35S from cysteine, methionine, and sodium sulfate was incorporated into monobactam by Acetobacter sp. Cell-free extracts of all three organisms were shown to possess cysteine desulfhydrase activity. In Acetobacter sp., this activity was constitutive, required pyridoxal phosphate, and had a pH optimum of 9.5. Extensive loss of 3H from L-[3-3H]cysteine was seen upon desulfhydration; no evidence of serine formation was found. Active sulfate was formed in cell-free extracts of A. radiobacter, and, since inorganic sulfur was used by all three organisms, it is likely that the sulfamate group of monobactams is produced via active sulfate.

Biosynthesis of monobactam compounds: origin of the carbon atoms in the beta-lactam ring.

The biosynthesis of monobactams by strains of Chromobacterium violaceum, Acetobacter sp., and Agrobacterium radiobacter was studied. Monobactams were produced during logarithmic growth by C. violaceum and Acetobacter sp. and during late log growth on glycerol and in stationary phase by A. radiobacter. The addition of various amino acids failed to significantly stimulate monobactam production in any of the producing organisms. Several 14C-amino acids and pyruvate were incorporated in vivo into monobactams. Serine, glycine, and cysteine were better incorporated than alanine or aspartate, whereas an excess of nonradioactive serine depressed the incorporation of labelled cysteine, glycine, and pyruvate. A comparison of [1-14C] glycine and [2-14C] glycine incorporation data suggests that glycine was first converted to serine. With a mixture of [U-14C[serine and [3-3H]serine, C. violaceum synthesized a monobactam with a complete retention of tritium, whereas with a [U-14C] cystine and [3-3H] cystine mixture, there was an extensive loss of C-3 tritium. Acetobacter sp. and A. radiobacter also utilized the double-labeled serine without the loss of tritium in their respective monobactams. It appears, therefore that in the three organisms, the carbon atoms of the beta-lactam ring of the monobactam are derived directly from serine without the loss of the C-3 hydrogen atoms, probably by an SN2 ring closure mechanism. With [methyl-14C] methionine, most of the radioactivity in the monobactam from Acetobacter sp. was in the methyl moiety of the beta-lactam ring methoxyl group.