Macquarimicins, microbial metabolites from Micromonospora. I. Discovery, taxonomy, fermentation and biological properties.

A novel series of microbial metabolites were discovered in fermentation broths of two soil isolates. Both cultures were identified as strains of Micromonospora chalcea. Production of the metabolites, named macquarimicins, was monitored by an HPLC assay. A seven-day fermentation yielded 27 mg/liter of macquarimicin A. With MICs of 50 to 100 micrograms/ml, macquarimicin A has only very low activity against strains of Bacteroides and other anaerobes. Macquarimicin B has inhibitory activity against the leukemia cell line P-388.

Tirandalydigin, a novel tetramic acid of the tirandamycin-streptolydigin type. I. Taxonomy of the producing organism, fermentation and biological activity.

Tirandalydigin is a new tetramic acid antibiotic which was discovered in a screen designed to find compounds with activity against pathogenic anaerobic bacteria. It was named tirandalydigin because it possesses structural features that are common to both tirandamycin and streptolydigin. The producing culture, strain AB 1006A-9, is a Streptomyces and was compared to the streptomycetes that synthesize tirandamycin and streptolydigin. It is closely related to the former culture and was named Streptomyces tirandis subsp. umidus. Tirandalydigin has MICs in the range of 0.5 to 32 micrograms/ml against many pathogenic anaerobes, streptococci, enterococci and legionellae.

Altromycins, novel pluramycin-like antibiotics. I. Taxonomy of the producing organism, fermentation and antibacterial activity.

The altromycins are novel anthraquinone-derived antibiotics related to the pluramycins. They are produced by an actinomycete, AB 1246E-26, which was isolated from a South African bushveld soil. The altromycins have Gram-positive antibacterial activity with MICs of 0.2 to 3.12 micrograms/ml against Streptococci and Staphylococci.

Pacidamycins, a novel series of antibiotics with anti-Pseudomonas aeruginosa activity. I. Taxonomy of the producing organism and fermentation.

The pacidamycins are a new complex of nucleosidyl-peptide antibiotics with highly specific activity against Pseudomonas aeruginosa. They are produced by Streptomyces coeruleorubidus AB 1183F-64 which was isolated from a soil sample collected at Offenburg in the FRG. The mature spore masses of the producing organism are greenish gray to blue, and the spore chains are arranged in spirals. After the structures of the pacidamycins were determined, the fermentation medium was supplemented with component amino acids. This resulted in the directed biosynthesis of several members of the complex. The overall antibiotic recovered was increased from 1 approximately 2 mg/liter to more than 100 mg/liter through a combination of strain selection, medium manipulation and amino acid feeding experiments.

Coumamidines, new broad spectrum antibiotics of the cinodine type. I. Discovery, taxonomy of the producing organism and fermentation.

Coumamidines are water-soluble basic antibiotics related to the glycocinnamoylspermidines. They are produced by a soil isolate designated Saccharopolyspora sp. AB 1167L-65. The coumamidines have broad spectrum activity and were selected in a screen for substances which inhibit Pseudomonas aeruginosa.

Phenelfamycins, a novel complex of elfamycin-type antibiotics. I. Discovery, taxonomy and fermentation.

Phenelfamycins A, B, C, E, F and unphenelfamycin have been discovered in the fermentation broth of two soil isolates, designated AB 999F-80 and AB 1047T-33. These isolates were identified as strains of Streptomyces violaceoniger. The antibiotics were selected for their activity against anaerobic bacteria.

Arizonins, a new complex of antibiotics related to kalafungin. I. Taxonomy of the producing culture, fermentation and biological activity.

The arizonins, a novel complex of antibiotics related to kalafungin, were discovered in the fermentation broth of Actinoplanes sp. AB660D-122. Comparative taxonomic studies indicated that the culture is a new species and therefore has been designated Actinoplanes arizonaensis sp. nov. Two members of the complex, arizonins A1 and B1, exhibit moderate to potent in vitro antimicrobial activity against pathogenic strains of Gram-positive bacteria.

Coloradocin, an antibiotic from a new Actinoplanes. I. Taxonomy, fermentation and biological properties.

Coloradocin was discovered in a screen for anti-anaerobe activity. The producing organism was determined to be a new species of Actinoplanes, designated Actinoplanes coloradoensis sp. nov. Coloradocin inhibits Bacteroides, Clostridium and other anaerobes. It does not inhibit most aerobic bacteria but is effective against Neisseria gonorrhoeae and Haemophilus influenzae. Coloradocin has low acute toxicity.

Tiacumicins, a novel complex of 18-membered macrolide antibiotics. I. Taxonomy, fermentation and antibacterial activity.

A complex of 18-membered macrolide antibiotics has been discovered in the fermentation broth of strain AB718C-41. The producing culture, isolated from a soil sample collected in Hamden, Connecticut, was identified as a strain of Dactylosporangium aurantiacum and was designated D. aurantiacum subsp. hamdenesis subsp. nov. The antibiotic complex was produced in a New Brunswick 150-liter fermentor using a medium consisting of glucose, soybean oil, soybean flour, beef extract and inorganic salts. Several of the antibiotics were active against sensitive and multiple antibiotic-resistant strains of pathogenic Gram-positive bacteria.

Abbeymycin, a new anthramycin-type antibiotic produced by a streptomycete.

A new antibiotic, abbeymycin, has been isolated from Streptomyces sp. AB-999F-52. The structure of abbeymycin was assigned on the basis of NMR, mass spectrometric and UV spectral data. Abbeymycin has weak activity against a limited number of anaerobic bacteria.

Benzanthrins A and B, a new class of quinone antibiotics. I. Discovery, fermentation and antibacterial activity.

Nocardia lurida has been shown to produce two novel quinone antibiotics, benzanthrins A and B. The antibiotics were discovered in concentrated butanol extracts of fermentation broths and were separated by TLC and HPLC. Benzanthrins A and B were produced in a fermentation medium consisting of glucose, yeast, selected peptones and CaCO3. The antibiotics were present primarily at 66 hours in shake flask fermentations and from 66 to 162 hours in 14-liter fermentors. Benzanthrins A and B inhibited a number of Gram-positive pathogenic bacteria but were inactive against Gram-negative bacteria.

Spenolimycin, a new spectinomycin-type antibiotic. I. Discovery, taxonomy and fermentation.

Spenolimycin, a new spectinomycin-type antibiotic, was discovered in the fermentation broth of a new actinomycete named Streptomyces gilvospiralis sp. nov. strain AB634D-177. Although a small amount of spectinomycin is coproduced by strain AB634D-177, the culture is different from other known spectinomycin-producing actinomycetes. Spenolimycin was obtained by conventional submerged culture in 14-liter fermentors with a peak antibiotic titer of 140 micrograms/ml.

Microbial hydroxylation of 5-anilino-1,2,3,4-thiatriazole.

Two hundred eighty-five fungi, including 100 basidiomycetes and 35 yeasts, 75 actinomycetes, and 40 bacteria were screened for their ability to convert 5-anilino-1,2,3,4-thiatriazole (AT) to 5-(p-hydroxyanilino)-1,2,3,4-thiatriazole (p-HT). Eleven cultures were found that formed p-HT, which was isolated and whose structure was determined. Aspergillus tamarii NRRL 3280 formed 8.6 g of p-HT/liter from 10 g of AT/liter (78.9% conversion) in shaken flasks and 4.57 g of p-HT/liter from 6 g of AT/liter (69.8% conversion) in 30-liter fermentors. Washed cells of A. tamarii NRRL 3280 also carried out this conversion. 5-(o-hydroxyanilino)-1,2,3,4-thiatriazole (o-HT) was identified as a second product formed by Aspergillus terreus NRRL 1960.

Microbial conversion of acetanilide to 2'-hydroxyacetanilide and 4'-hydroxyacetanilide.

Approximately 700 cultures of various types were examined for their ability to hydroxylate acetanilide. The major product formed by unidentified Streptomyces species RJTS-539 was identified as 4'-hydroxyacetanilide (N-acetyl-p-aminophenol). This culture gave a peak yield of 405 mg per liter from 1,000 mg of acetanilide per liter. Considerably lower yields of 4'-hydroxyacetanilide were isolated from S. cinnamoneus NRRLB-1285. The major conversion product of acetanilide formed by Amanita muscaria F-6 was identified as 2'-hydroxyacetanilide, with a peak yield of 433 mg per liter from 1,000 mg per liter of substrate. A small amount of 4'-hydroxyacetanilide was also formed. Six other Streptomyces cultures formed small amounts of one or two products identical or similar to 2'-hydroxyacetanilide or 4'-hydroxyacetanilide as determined by thin-layer chromatography and ultraviolet spectra.