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.

Lanomycin and glucolanomycin, antifungal agents produced by Pycnidiophora dispersa. I. Discovery, isolation and biological activity.

The antifungal agents lanomycin and glucolanomycin were isolated from Pycnidiophora dispersa. The compounds were active against species of Candida and dermatophytes but were inactive against Aspergillus fumigatus and Gram-positive and Gram-negative bacteria. The compounds inhibited the cytochrome P-450 enzyme lanosterol 14 alpha-demethylase, and are believed, therefore, to have a mode of action similar to the azole and bis-triazole class of antifungal agents.

Janthinocins A, B and C, novel peptide lactone antibiotics produced by Janthinobacterium lividum. I. Taxonomy, fermentation, isolation, physico-chemical and biological characterization.

Janthinocins A, B and C are novel antibacterial agents produced by Janthinobacterium lividum. They were isolated from fermentation broths and characterized by UV, IR, NMR and mass spectroscopy. They are cyclic decapeptide lactones with marked activity against aerobic and anaerobic Gram-positive bacteria and are 2 to 4 times more potent in vitro than vancomycin. Janthinocins A and B were also found to be effective in a Staphylococcus aureus systemic infection in mice.

Lysobactin, a novel antibacterial agent produced by Lysobacter sp. I. Taxonomy, isolation and partial characterization.

A new antibacterial agent, lysobactin, has been isolated from a species of Lysobacter (ATCC 53042). The antibiotic was recovered from the Lysobacter cell mass by extraction and reversed phase chromatography. Lysobactin is a dibasic peptide with marked activity against Gram-positive aerobic and anaerobic bacteria.

Aerocavin, a new antibiotic produced by Chromobacterium violaceum.

A new antibiotic, aerocavin, has been isolated from fermentation broths of a non-pigmented strain of Chromobacterium violaceum. The structure 1 was deduced from its spectroscopic properties and X-ray diffraction analysis. Aerocavin exhibits activity in vitro against Gram-positive and Gram-negative bacteria.

Catacandins, novel anticandidal antibiotics of bacterial origin.

Two novel antibiotics, catacandin A and catacandin B, were isolated from the fermentation broth of the bacterium, Lysobacter gummosus, by extraction and adsorption, reverse-phase and gel filtration chromatography. On the basis of their physico-chemical properties, they are acyltetramic acids that are easily distinguishable from others in this class. Catacandin A and catacandin B possess good anticandidal activity.

Phenacein--an angiotensin-converting enzyme inhibitor produced by a streptomycete. I. Taxonomy, fermentation and biological properties.

Phanacein, 3,6-dihydroxy-1-phenazinecarboxylic acid, was a specific angiotensin-converting enzyme (ACE) inhibitor isolated from a member of the Streptomyces tanashiensis-zaomyceticus group. Phenacein acted as a pure competitive inhibitor with a Ki of 0.58 microM. ACE inhibition could be reversed by Zn++, but not by Co++, Ca++, or Mg++; therefore, phenacein may chelate the active site zinc of ACE. However, other zinc-containing enzymes were not inhibited at high phenacein concentrations. Phenacein exhibited weak activity against Gram-positive bacteria, but was not active against Candida sp. or Gram-negative organisms.

Cepacin A and cepacin B, two new antibiotics produced by Pseudomonas cepacia.

Two new acetylenic antibiotics, cepacins A and B, have been isolated from the fermentation broth of Pseudomonas cepacia SC 11,783 and assigned structures 1 and 2. Cepacin A has good activity against staphylococci (MIC 0.2 micrograms/ml) but weak activity against streptococci (MIC 50 micrograms/ml) and the majority of Gram-negative organisms (MIC values 6.3 approximately greater than 50 micrograms/ml). Cepacin B has excellent activity against staphylococci (MIC less than 0.05 micrograms/ml) and some Gram-negative organisms (MIC values 0.1 approximately greater than 50 micrograms/ml).

SQ 28,332, a new monobactam produced by a Flexibacter sp. Taxonomy, fermentation, isolation, structure determination and biological properties.

A new monobactam SQ 28,332 has been isolated from fermentations of a Flexibacter sp. and the structure 3 was deduced from its spectroscopic properties. SQ 28,332 exhibits weak antibacterial activity.

Two new monobactam antibiotics produced by a Flexibacter sp. I. Taxonomy, fermentation, isolation and biological properties.

Two new beta-lactam antibiotics, namely SQ 28,502 and SQ 28,503, have been isolated from fermentations of a Flexibacter sp. They are demethoxy monobactams with oligopeptide side chains and have molecular weights of 1,462 and 1,446, respectively. These beta-lactams show a high degree of stability to a variety of beta-lactamases and act as potent irreversible inactivators of P99 beta-lactamase from Enterobacter cloacae. They exhibit weak antibacterial activity.

Distribution of beta-lactam and beta-lactone producing bacteria in nature.

Over one million bacteria were isolated from a large variety of soil, plant and water samples collected from different environments and examined in an extremely sensitive and highly specific screen for beta-lactam production. A group of seven related monocyclic beta-lactams (monobactams) were isolated from strains representing four genera-Agrobacterium, Chromobacterium, Gluconobacter and Pseudomonas. Monobactam-producing strains of Agrobacterium and Pseudomonas were isolated only rarely. Producing strains of Chromobacterium were isolated from a relatively limited number of habitats while the Gluconobacter strains appeared to be widespread in nature. In addition, three closely related beta-lactone-containing molecules were isolated from strains representing three genera-Arthrobacter, Bacillus and Pseudomonas. The Bacillus and Pseudomonas strains were isolated infrequently but from a variety of samples. The producing strain of Arthrobacter was isolated only once.

SQ 26,180, a novel monobactam. I Taxonomy, fermentation and biological properties.

Strains of Chromobacterium violaceum, isolated from various environments, were found to produce a novel monocyclic beta-lactam antibiotic. The antibiotic, SQ 26,180 was weakly active against Gram-positive and Gram-negative bacteria with the exception of mutants hypersensitive to beta-lactam antibiotics. The compound was highly stable to beta-lactamases and acted as an inhibitor of the P99 enzyme from Enterobacter cloacae. SQ 26,180 showed affinity for penicillin-binding proteins 1a, 4 and 5/6 of Escherichia coli and inhibited R61 DD-carboxypeptidases.