Studies on the mechanism of action of A80915A, a semi-naphthoquinone natural product, as an inhibitor of gastric (H(+)-K+)-ATPase.

A semi-naphthoquinone natural product, A80915A, produced by Streptomyces aculeolatus was found to be a potent inhibitor of gastric (H(+)-K+)-ATPase, the enzyme responsible for acid secretion in the stomach. Enzyme activity was measured by potassium-stimulated hydrolysis of ATP or p-nitrophenolphosphate with enzyme prepared from the stomach fundic mucosa of pigs. Concentration-dependent inhibition was observed with an IC50 of about 2-3 microM for both ATPase and p-nitrophenylphosphatase.

A54145 a new lipopeptide antibiotic complex: microbiological evaluation.

A54145 complex is made up of eight factors; A, A1, B, B1, C, D, E, and F which were active in vitro (MIC 0.25 approximately greater than 32 micrograms/ml) against Gram-positive aerobic organisms. The complex, factor B and B1 were found to be active against two strains of Clostridium perfringens.

A54145, a new lipopeptide antibiotic complex: microbial and chemical modification.

A54145 is a complex of acidic lipopeptide antibiotics produced by Streptomyces fradiae NRRL 18158, NRRL 18159, and NRRL 18160. Each antibiotic factor consists of a peptide core bearing an N-terminal acyl substituent. N-Lys-tert-BOC-protected A54145 complex was deacylated by Actinoplanes utahensis; three protected core peptides were isolated.

A54145, a new lipopeptide antibiotic complex: isolation and characterization.

A54145 is a complex of acidic lipopeptide antibiotics which are produced by Streptomyces fradiae and are active against Gram-positive bacteria. The A54145 complex was isolated by adsorption on Diaion HP-20 nonfunctionalized macroreticular resin and/or ion exchange on Amberlite IRA-68 anion exchange resin. Antibacterial factors A, A1, B, B1, C, D, E, and F were obtained in purified form by repeated preparative reverse phase HPLC on C8 and/or C18 bonded-phase supports.

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.

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.

[A retroperitoneal leiomyosarcoma--a case of non-concurrent double cancers with kidney cancer].

A retroperitoneal leiomyosarcoma in a 50-year-old man is reported. A laparotomy was performed on Dec. 17, 1987 and the tumor, weighing 120 g, was completely excised.

Synthesis of new analogs of echinocandin B by enzymatic deacylation and chemical reacylation of the echinocandin B peptide: synthesis of the antifungal agent cilofungin (LY121019).

The antifungal antibiotic, echinocandin B (ECB), was modified by a sequential procedure in which the initial step involved enzymatic removal of the native N-linoleoyl group from the N-terminus using an Actinoplanes utahensis culture. The resulting product, ECB nucleus, was reacylated using active esters or acid halides of various substituted acids to give a series of ECB analogs. These analogs possessed anti-Candida activity both in vitro and in vivo (mice).

Deacylation of echinocandin B by Actinoplanes utahensis.

Echinocandin B (ECB) is a lipopeptide antifungal agent produced by several species of Aspergillus. The lipid side chain of cyclic lipopeptides is known to be an important determinant of their antibiotic activity and toxicity. Deacylation of another lipopeptide antibiotic, A21978C, had formerly been accomplished with Actinoplanes utahensis.

[Case report of a second resection of rectal leiomyosarcoma due to recurrence after 10 years].

A leiomyosarcoma of the rectum is a rare disease, and cases of a recurrence are even more rare. Reported is the case of a patient who, in 1987, underwent a per sacral resection of a rectal tumor which was diagnosed as leiomyosarcoma. In 1987, after symptoms that showed that the patient's feces had become narrower, a recurrence of this tumor was diagnosed, so that the patient again underwent an abdominoperineal rectomy.

Deacylation of A21978C, an acidic lipopeptide antibiotic complex, by Actinoplanes utahensis.

A21978C, produced by Streptomyces roseosporus NRRL 11379, is an acidic lipopeptide antibiotic complex that inhibits Gram-positive bacteria. Individual factors of the complex possess an identical peptide core or "nucleus", and are differentiated by the distinctive fatty acid acyl group attached to the N-terminus of the nucleus. Certain members of the family Actinoplanaceae deacylated A21978C to yield the unaltered nucleus, which was then reacylated to form new analogs.

Enzymatic and chemical modifications of lipopeptide antibiotic A21978C: the synthesis and evaluation of daptomycin (LY146032).

The novel lipopeptide antibiotic A21978C complex is active against Gram-positive organisms. This complex consists of a common peptide nucleus with various lipid acyl groups at the N-terminus characteristic of each individual factor. The fatty acid acyl group is removed by incubation of the A21978C complex with Actinoplanes utahensis to give the peptide nucleus.

Structure elucidation of A58365A and A58365B, angiotensin converting enzyme inhibitors produced by Streptomyces chromofuscus.

A58365A and A58365B, angiotensin converting enzyme inhibitors isolated from the culture filtrate of Streptomyces chromofuscus NRRL 15098, are homologous compounds of molecular formulas C12H13NO6 and C13H15NO6. The molecular similarities of the two inhibitors were established by comparison of their 1H NMR, 13C NMR, and UV spectra. Catalytic hydrogenation of A58365A led to a tetrahydro-deoxy derivative, C12H17NO5; extensive 1H NMR decoupling studies at 360 MHz allowed all the non-exchangeable protons of the derivative to be connected in a continuous substructure.

Method for the detection and quantitation of chitinase inhibitors in fermentation broths; isolation and insect life cycle effect of A82516.

A new method of screening for chitinase inhibitors in crude fermentation broths as a means of discovering new insecticidal leads has been developed. In this procedure soluble Remazol brilliant violet 5R dye-coupled chitin degradation products released from insoluble chitin azure substrate by hydrolysis with Streptomyces griseus chitinase are filtered in 0.45 micron Millititer HA 96 well filtration plates and collected in 96 well microtiter plates.

A21978C, a complex of new acidic peptide antibiotics: isolation, chemistry, and mass spectral structure elucidation.

A21978C, produced by Streptomyces roseosporus, NRRL 11379, is a complex of new acidic lipopeptolide antibiotics which inhibits Gram-positive bacteria. HPLC separation of the various components from the purified complex resulted in the isolation of A21978C1, -C2 and -C3 (major components) and -C4, -C5, and -C0 (minor components). Each of these components was fermented with cultures of Actinoplanes utahensis (NRRL 12052) to give the identical inactive peptide ("A21978C nucleus") by removal of the fatty acid acyl groups from the N-terminus.

Preparation and evaluation of 3,4''-ester derivatives of 16-membered macrolide antibiotics related to tylosin.

A large group of ester derivatives of tylosin-related macrolides was prepared in which the hydroxyl groups at C-3 and C-4'' were acylated by either chemical or biochemical methods. Most of the derivatives exhibited excellent in vitro antimicrobial activity. However, only the 3,4''-diacyl derivatives of tylosin and macrocin showed any significant improvements of in vivo efficacy against experimental infections in rodents.

Isolation of A58365A and A58365B, angiotensin converting enzyme inhibitors produced by Streptomyces chromofuscus.

A58365A and A58365B, angiotensin converting enzyme inhibitors, were isolated from the culture filtrate of Streptomyces chromofuscus NRRL 15098. A58365A and A58365B are homologous nitrogen-containing bicyclic structures of molecular formulae C12H13NO6 and C13H15NO6.

Microbial transformation of A23187, a divalent cation ionophore antibiotic.

A23187 is an ionophore antibiotic that forms dimeric complexes with divalent cations such an Mn2+ and Ca2+. Over 200 randomly selected soil microorganisms were incubated with A23187. None of these cultures was capable of transforming this compound.

Microbiological transformations of nabilone, a synthetic cannabinoid.

A screening program was conducted to find microorganisms that modify the synthetic cannabinoid nabilone. After purification, the products from three cultures were analyzed by spectral methods to determine their chemical structures. An optically active 9S-hydroxy-6aR,10aR-trans cannabinoid was isolated from a culture of an unidentified soil bacterium designated A24007.

Microbiological transformation of cannabinoids.

Microorganisms were screened for their ability to modify 2 synthetic cannabinoid substrates (I and II). Structure analyses revealed that microorganisms transformed the substrates by (a) primary oxidation of the side chain, beta-oxidation of the side chain, ketone formation on the side chain or cyclohexene ring, (b) secondary hydroxylation on the side chain, (c) aromatization of the cyclohexene ring, and (d) tertiary hydroxylation at the b/c ring juncture.

Microbiological transformations of delta6a10a-tetrahydrocannabinol.

A screening program was conducted to find microorganisms that catalyze transformation reactions with cannabinoids. Three hundred fifty-eight cultures, consisting of 97 bacteria, 175 actinomycetes, and 86 molds, were incubated in media containing 0.5 mg of Delta(6a,10a)-tetrahydrocannabinol (Delta(6a,10a)-THC) per ml.

Immobilization of a cephalosporin acetylesterase by containment within an ultrafiltration device.

A cephalosporin acetylesterase produced by Bacillus subtilis catalyzes the deacetylation of 7-aminocephalosporanic acid (7-ACA). Previous reports from our laboratory described the kinetic constants that characterize the reaction: Km = 2.8 X 10(-3)M, Kia acetate = 5 X 10(-2)M, and Kid deacetyl-7-ACA = 3.

De-esterification of cephalosporin para-nitrobenzyl esters by microbial enzymes.

Bacteria and actinomycetes were screened for esterase enzymes capable of removing the para-nitrobenzyl ester from cephalosporins. An esterase preparation from Bacillus subtilis was used to prepare cephalexin and 7-ADCA from the corresponding para-nitrobenzyl esters.

Physical properties and kinetic behavior of a cephalosporin acetylesterase produced by Bacillus subtilis.

An esterase that deacetylates cephalosporins was recovered from the supernatant of a Bacillus subtilis culture. It was partially purified by ammonium sulfate fractionation and ultrafiltration. The enzyme had a temperature optimum between 40 and 50 C and a pH optimum of 7.