ABSTRACT
A glycolipid was found in a strain of Nocardia caviae. It consists of glucose, myristic, palmitic and stearic acids and a polyhydroxylated acid. The structure of this hydroxyacid was demonstrated by the identification of the product glycerol after LiA1H4 reduction of the glycolipid methyl ester and subsequent hydrolysis, by comparison of the infrared spectra of the hydroxyacid and glyceric acid, by gas chromatography of acetylated methyl and ethyl esters of the polyhydroxylated acid and of standard glyceric acid and by mass spectrometry of the diacetylated methyl ester. The hydroxyacid from the glycolipid is D(-)glyceric acid, a compound rarely found amongst natural products.
Subject(s)
Glyceric Acids/analysis , Nocardia/analysis , Glucose/analysis , Glycolipids/analysis , Hydroxy Acids/analysis , Myristic Acids/analysis , Palmitic Acids/analysis , Stearic Acids/analysisABSTRACT
3-Ketosteroid-delta 1-dehydrogenase from Nocardia corallina catalyzes transhydrogenation of 3-keto-4-ene-steroid to 3-keto-1,4-diene-steroid e.g., progesterone to 1,4-androstadiene-3,17-dione. The reaction proceeded linearly at first and then soon slowed down owing to equilibration. The turnover number of this reaction was of the same magnitude as that of the dehydrogenation of 3-keto-4-ene-steroid. The pH optimum was 8.4, which is lower than that of the dehydrogenase reaction. The enzyme has a wide specificity for hydrogen acceptor steroids. The Km' and Kmax' values for these steroids and the values of the corresponding 3-keto-4-ene-steroids were compared. Kinetic studies of the steroid transhydrogenase reaction demonstrated a typical ping-pong mechanism. The enzyme oxidized 1,2-tritiated progesterone and transferred the tritium atoms to the reaction product, 4-androstene-3,17-dione, and water. Transhydrogenation in D2O resulted in the incorporation of a deuterium atom into the C2-position of 4-androstene-3,17-dione. The results indicate that the enzyme catalyzes C1, C2-trans axial abstraction of hydrogen atoms from progesterone, transfer of the 1 alpha-hydrogen to the C1-position of 1,4-androstadiene-3, 17-dione and release of the 2 beta-hydrogen to water. Reaction schemes based on the experimental results are proposed. The enzyme also catalyzes the reduction of 3-keto-1,4-diene-steroids with reduced benzyl viologen.
Subject(s)
Nocardia/enzymology , Oxidoreductases/metabolism , Androstadienes/metabolism , Benzyl Viologen , Deuterium , Hydrogen-Ion Concentration , Kinetics , Mass Spectrometry , Nocardia/analysis , Oxidation-Reduction , PhotometryABSTRACT
We have previously reported that mycolyl glycolipids from Nocardia rubra such as glucose or trehalose mycolates induced granuloma formation in mice. The structure of the carbohydrate moiety of the mycolyl glycolipids influenced the granuloma forming activity profoundly. Here, we have examined the macrophage-chemotactic activity in the culture supernatants stimulated with various glycolipids differing in carbohydrate moiety (trehalose 6,6'-dimycolate, or TDM; glucose monomycolate, or GM; mannose monomycolate, or MM; and fructose monomycolate, or FM). A distinctive chemotactic activity was detected with TDM or GM, but, little or none with MM or FM.
Subject(s)
Chemotactic Factors/metabolism , Glycolipids/pharmacology , Macrophages/drug effects , Mycolic Acids/pharmacology , Animals , Cord Factors/pharmacology , Glycolipids/isolation & purification , In Vitro Techniques , Macrophages/metabolism , Male , Mice , Mice, Inbred ICR , Mycolic Acids/isolation & purification , Nocardia/analysisABSTRACT
B-Factor, 3'-(1-butylphosphoryl)adenosine, which was isolated from yeast extract, is an inducer of rifamycin production in a rifamycin non-producing Nocardia mutant. Feeding of B-factor to the mutant culture demonstrated that the induction process was triggered during early stationary phase. Rifamycin production in the mutant was also induced by an exogenous supply of 3-amino-5-hydroxybenzoic acid, an intermediate of the antibiotic pathway, suggesting that a step upstream from the intermediate is regulated by B-factor. B-Factor analogues, i.e., alkylesters of 3'-AMP with alkyl side chains of C(2) approximately C(12) and n-butyl esters of 3'-GMP and 2'-AMP all showed the B-factor activity. Among these n-octyl ester of 3'-AMP showed the lowest effective concentration of approximately 3 x 10(-10) M. An intrinsic substance of the Nocardia sp. with potent B-factor activity and a UV absorption maximum at 260 nm was isolated from the cells of the parental strain.
Subject(s)
Adenosine Monophosphate/analogs & derivatives , Nocardia/metabolism , Rifamycins/biosynthesis , Adenosine Monophosphate/isolation & purification , Adenosine Monophosphate/pharmacology , Mutation , Nocardia/analysisABSTRACT
Actinomycete strain M-53, a new soil isolate, was found to produce four quinone-type antibiotics. Antibiotic sakyomicin components, A, B, C and D were isolated from the fermentation broth of strain M-53 by XAD-2 column chromatography, silica gel column chromatography and Sephadex LH-20 column chromatography. The components are active against Gram-positive bacteria. Strain M-53 was identified as a strain of genus Nocardia.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Benzoquinones , Microbial Sensitivity Tests , Nocardia/analysis , Quinones/isolation & purification , Quinones/pharmacology , X-Ray DiffractionABSTRACT
The structures of 3-hydroxyrifamycin S and six further novel ansamycins isolated from the recombinant strain R-21 of Nocardia mediterranei were identified by spectroscopic methods. Three types of structure were distinguished: Type 1: Ansamycins of the rifamycin S type Type 2: Ansamycins of the rifamycin G type Type 3: Ansamycins of the rifamycin W type.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Nocardia/analysis , Rifamycins/isolation & purification , Bacteria/drug effects , Lactams, Macrocyclic , Microbial Sensitivity Tests , Nocardia/genetics , Recombination, Genetic , Structure-Activity RelationshipABSTRACT
An unidentified Nocardia sp. (SK&F-AAJ-193) was isolated and found to produce actinoidin A and a novel analog which we have named actinoidin A2. This new glycopeptide antibiotic differs from actinoidin A by the presence of rhamnose instead of acosamine. This analog was isolated using Dianion HP-20 resin followed by a specific glycopeptide affinity column (Affigel-10-D-Ala-D-Ala). The purification was accomplished using preparative ion-pairing chromatography. Actinoidin A2 is active against Staphylococcus aureus and coagulase-negative Staphylococci although it is less potent than actinoidin A.
Subject(s)
Nocardia/analysis , Vancomycin/analogs & derivatives , Animals , Chemical Phenomena , Chemistry, Physical , Chromatography , Fermentation , Gram-Positive Bacteria/drug effects , Mice , Microbial Sensitivity Tests , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Staphylococcus aureus/drug effects , Vancomycin/biosynthesis , Vancomycin/isolation & purification , Vancomycin/pharmacologyABSTRACT
LL-BM123beta, gamma1 and gamma2 are three new antibiotics produced by fermentation of an unidentified species of Nocardia. These strongly basic, water soluble compounds were isolated from the culture filtrate by CM-Sephadex ion-exchange and carbon chromatography. All three antibiotics are active against both gram-positive and gram-negative bacteria. A mixture of LL-BM123 gamma1 and gamma2 is more active than the beta component but generally less active than gentamicin.
Subject(s)
Anti-Bacterial Agents/analysis , Spermidine/analogs & derivatives , Animals , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Bacterial Infections/drug therapy , Chemical Phenomena , Chemistry, Physical , Female , Mice , Nocardia/analysis , Spermidine/analysis , Spermidine/pharmacologyABSTRACT
New antibiotics spirocardins A and B were isolated from the culture broth of an actinomycete isolated from a soil sample collected near Lake Hibara, Fukushima Prefecture, Japan. The producing strain was classified as Nocardia sp. SANK 64282. The antibiotics were isolated from the culture filtrate by solvent extraction and purified further by silica gel and preparative reverse phase column chromatography. They were primarily active against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus and limited species of Gram-negative bacteria such as Bacteroides fragilis and Klebsiella pneumoniae. They were also moderately active against several species of Mycoplasma. The molecular formulae of spirocardins A and B were C20H30O6 and C20H32O6, respectively. From their physico-chemical characteristics they were revealed to be diterpenoid antibiotics with closely related structures and the former was easily converted to the latter by the reduction with NaBH4.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Diterpenes/isolation & purification , Anti-Bacterial Agents/pharmacology , Chemical Phenomena , Chemistry , Diterpenes/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Microbial Sensitivity Tests , Nocardia/analysis , Structure-Activity RelationshipABSTRACT
Nocardicin A, a new monocyclic beta-lactam antibiotic, exerts a comparatively potent antimicrobial activity against gram-negative organisms, especially Pseudomonas aeruginosa, the indole-positive and indole-negative Proteus groups (except Pr. morganii), Serratia marcescens and the Neisseria groups. The in vitro antimicrobial activity of nocardicin A against clinical isolates of Ps. aeruginosa was about twice that of carbenicillin. The mean MICs of nocardicin A for Pr. mirabilis, Pr. rettgeri and Pr. inconstans ranged from 3.13 to 12.5 microgram/ml and were 25 similar to 50 microgram/ml for Pr. vulgaris. Nocardicin A in concentrations of 12.5 similar to 50 microgram/ml inhibited 30 strains (48 percent) of S. marcescens usually resistant to beta-lactam antibiotics. However, nocardicin A had no significant in vitro activity against Staphylococci and Escherichia coli. No cross-resistance was seen between nocardicin A and other beta-lactam antibiotics. This antibiotic was stable to beta-lactamase. The in vitro activity of nocardicin A against Ps. aeruginosa and Pr. mirabilis was greatly influenced by the assay media used. Nocardicin A was bactericidal and appeared to act synergistically with serum bactericidal factors against Ps. aeruginosa and with polymorphonuclear leukocytes against Ps. aeruginosa, E. coli and Pr. vulgaris. The bactericidal activity of nocardicin A against the above 3 organisms, therefore, increased markedly in the presence of fresh serum and polymorphonuclear leukocytes.