Amycolatopsis alba sp. nov., isolated from soil.

A new Amycolatopsis species isolated from soil produces a new glycopeptide antibiotic related to vancomycin. Traditional taxonomic methods and contemporary fatty acid analysis techniques were used to establish the position of this species. The hyphae fragment extensively when the organism is cultured in liquid media. The organism is characterized by white aerial hyphae that bear long chains of cylindrical conidia. The reverse side is yellowish brown; a faint light brown soluble pigment is occasionally produced. The organism has a type IV cell wall (meso-diaminopimelic acid), a type A whole-cell sugar pattern, and a type PII phospholipid pattern. Mycolic acids are not present in whole-cell hydrolysates. The major menaquinone is MK-9(H4); there is also a minor amount of MK-8(H4). The name proposed for this new species is Amycolatopsis alba. The type strain is strain A83850 (= NRRL 18532).

A10255, a complex of novel growth-promoting thiopeptide antibiotics produced by a strain of Streptomyces gardneri. Taxonomy and fermentation studies.

A10255 is a complex of new thiopeptide antibiotics characterized structurally by a cyclic peptide core to which is attached a side chain composed of dehydroalanine moieties. The complex contained 80-85% factor B, 15-20% factor G, and trace amounts of factors C, D, E, F, H, and J. Taxonomic studies indicated the producing microorganism to be a strain of Streptomyces gardneri. The major portion of the antibiotic produced remained associated with the mycelial biomass, from which it was extracted with polar solvents such as aqueous methanol or aqueous acetone. Initial A10255 yields of < 2 micrograms/ml were increased to over 300 micrograms/ml in stirred reactors through strain selection, nutritional studies, and conversion of the batch fermentation to a fed-batch mode.

A54145, a new lipopeptide antibiotic complex: discovery, taxonomy, fermentation and HPLC.

A54145 is a complex of new lipopeptide antibiotics that inhibits Gram-positive bacteria and acts as a growth promotant for broiler chicks. Eight factors; A, B, C, D, E, F, A1 and B1; have been isolated and characterized. They contain four similar peptide nuclei, each of which is acylated with either an 2-decanoyl, n-decanoyl, or undecanoyl side chain. Taxonomic studies ascertained that the producing microorganism was a strain of Streptomyces fradiae. Fermentation studies determined that superior antibiotic yields were obtained in stirred bioreactors in a soybean flour-molasses medium employing a continuous glucose feed. These findings, interwoven with the selection of hyper-productive mutants, increased fermentation yields from less than 50 micrograms/ml to more than 1 mg/ml. An analytical HPLC system was developed for the identification and subsequent quantitation of each factor of the A54145 complex.

A80915, a new antibiotic complex produced by Streptomyces aculeolatus. Discovery, taxonomy, fermentation, isolation, characterization, and antibacterial evaluation.

New semi-naphthaquinone antibiotics A80915A, B, C, and D were isolated from the fermented broth of Streptomyces aculeolatus A80915 (NRRL 18422). Factors A and C, present in both the broth filtrate and mycelial methanol extract, and factors B and D, found predominantly in the broth filtrate, were recovered by extraction with ethyl acetate. Purification of the individual factors was accomplished by preparative reverse phase high performance liquid chromatograph on C18 bonded silica supports. Factors A through D show antimicrobial activity against Gram-positive aerobic and anaerobic organisms in vitro. Mechanism of action studies demonstrated nearly complete inhibition of macromolecular biosynthesis (protein, RNA, DNA, and cell wall) by A80915 factors A through D. A less highly cyclized semi-naphthaquinone, A80915 factor G, was isolated from the broth of the strain fermented in an alternate medium.

Actinomadura fibrosa sp. nov. isolated from soil.

A new species of the genus Actinomadura which belongs to the Actinomadura madurae group of Goodfellow et al. was isolated from soil collected in Togo, West Africa. Traditional taxonomic methods plus contemporary fatty acid analysis techniques were used to establish the position of this species. Both physiological characteristics and fatty acid composition differentiate this strain from previously described species. This culture produces a new polyether antibiotic. It is characterized by the production of white to pink aerial hyphae on a limited number of media. The aerial hyphae appear asporogenous, forming thick fibers and projections instead of true spores. The reverse side is a distinctive reddish orange. This organism is resistant to 5% NaCl and grows at temperatures between 20 and 45 degrees C. Whole cells contain meso-diaminopimelic acid, galactose, glucose, mannose, madurose, phosphatidylinositol, and diphosphatidylglycerol. The menaquinones detected were MK-9(H6) and minor amounts of MK-9(H8). The name proposed for this new species is Actinomadura fibrosa; the type strain is strain NRRL 18348.

16-Deethylindanomycin (A83094A), a novel pyrrole-ether antibiotic produced by a strain of Streptomyces setonii. Taxonomy, fermentation, isolation and characterization.

16-Deethylindanomycin (A83094A) is a novel pyrrole-ether antibiotic produced by a strain of Streptomyces setonii. The antibiotic, which is structurally similar to indanomycin (X-14547A), is active in vitro against Gram-positive bacteria as well as coccidia.

A83586C, a new depsipeptide antibiotic.

A culture identified as Streptomyces karnatakensis was found to produce a novel cyclic hexadepsipeptide antibiotic designated A83586C. The structure was elucidated by X-ray crystallography, and full 1H and 13C NMR assignments are reported. The absolute configuration was confirmed by the detection of D-threonine in the acid hydrolysate of A83586C. A83586C had potent Gram-positive activity in vitro but lacked in vivo efficacy in mice.

A47934, a novel glycopeptide-aglycone antibiotic produced by a strain of Streptomyces toyocaensis taxonomy and fermentation studies.

A47934, a novel glycopeptide-aglycone antibiotic, is produced by a strain of Streptomyces toyocaensis, NRRL 15009. A47934 is unique among reported glycopeptides in that it contains a sulfate ester. Like several other glycopeptides, the majority of the A47934 produced remained associated with the producing biomass, from which it could be released into aqueous media by alkalization. Antibiotic biosynthesis was depressed when initial levels of phosphate phosphorus in the medium exceeded the normal level of 35 micrograms/ml. Enrichment of the fermentation medium with tyrosine depressed A47934 yields while enrichment with p-hydroxyphenylglycine or p-hydroxyphenylglyoxylic acid stimulated antibiotic biosynthesis.

Angiotensin converting enzyme inhibitors produced by Streptomyces chromofuscus. Discovery, taxonomy and fermentation.

Culture A58365.1, NRRL 15098, identified as a new strain of Streptomyces chromofuscus, was found to produce two novel angiotensin converting enzyme (ACE) inhibitors, A58365A and A58365B. Fermentation medium studies afforded an increase in ACE inhibitor titers from less than 1 microgram/ml to greater than 20 micrograms/ml. Proline was the obligatory supplement for ACE inhibitor biosynthesis.

A41030, a complex of novel glycopeptide antibiotics produced by a strain of Streptomyces virginiae. Taxonomy and fermentation studies.

A41030 is a complex of novel glycopeptide antibiotics produced by a culture isolated from a soil. Taxonomic studies have identified the microorganism, NRRL 15156, as a strain of Streptomyces virginiae. The major factor, A41030A, and three of the six minor factors are unique among glycopeptides in that they are naturally occurring aglycones, containing no neutral or amino sugars. The A41030 that was not spontaneously released into the fermentation broth could be released from the biomass into aqueous media at pH 10.5. In contrast to the vancomycin and N-demethylvancomycin fermentations, A41030 biosynthesis was stimulated by enriching the medium with K2HPO4 at a level of 1 mg/ml. Enrichment with putative precursors of the aglycone, however, did not increase the biosynthesis of A41030.

N-demethylvancomycin, a novel antibiotic produced by a strain of Nocardia orientalis. Taxonomy and fermentation.

A novel vancomycin analog, N-demethylvancomycin, is produced by a soil isolate collected in Yucatan, Mexico. Taxonomic studies indicated this microorganism, designated NRRL 15232, is a strain of Nocardia orientalis. Unlike some glycopeptide antibiotics, virtually none of the N-demethylvancomycin synthesized remained bound to the cells of the producing culture. Antibiotic production was markedly depressed by the addition of orthophosphate to the fermentation medium. Enrichment of the medium with tyrosine, p-hydroxyphenylglycine, p-hydroxyphenylglyoxylic acid, or leucine, all putative precursors of the aglycone, stimulated the biosynthesis of N-demethylvancomycin.