Production of antibiotic carbomycin from Streptomyces graminofaciens with high lipid content mutation.

The most important tools in killing and overcoming on the microbes and pathogens that cause diseases in medicine and/or in agriculture are the antibiotics. The discovery and synthesis of the microbial natural products or antibiotics has greatly developed genetically and biotechnologically quickly in the last decades. It is necessary to access this great genetic diversity by finding ways to increase the level of expression of these biosynthetic pathways. In this study, we carried out an improvement in the antibiotic production of weak Streptomyces graminofaciens strain NBR9 that has high lipid content; using Ultra-Violet irradiation mutagenesis. This strain was isolated from the Northern Region in the kingdom of Saudi Arabia and identified biochemically and confirmed genetically by sequencing of the 16S rRNA gene as Streptomyces graminofaciens NBR9; Accession No. (MN640578). The resultant mutant strain showed increasing in their antimicrobial activities. The methods and techniques used for the antibiotic extraction, purification, characterization and identification proved that the obtained antibiotic is same with antibiotic Carbomycin.

Sample preparation strategy for the simultaneous determination of macrolide antibiotics in animal feedingstuffs by liquid chromatography with electrochemical detection (HPLC-ECD).

A novel and suitable clean-up method that allows, for the first time, the simultaneous determination of a rather large number of macrolide antibiotics (erythromycin, rosamicin, spiramycin, tylosin, kitasamycin and josamycin in feedingstuffs by high performance liquid chromatography with electrochemical detection (HPLC-ECD) is presented in this work. The effectiveness of the developed clean-up method allows the quantification of the target macrolides in poultry feed using standard calibration curves instead of matrix matched standards, which overcomes the general problem of finding representative blanks. Furthermore an additional back extraction included in the sample preparation procedure allows the determination of an additional macrolide (oleandomycin) with detection limits, expressed as apparent concentration in poultry feed, ranging from 0.04 to 0.22 mg kg(-1) and relative standard deviation values ranging from 3.6 to 10.1% depending on the target analyte. Moreover, this additional step has been proven to enlarge the scope of the method by the extension of its applicability, at the target level of concentration, to other animal feedingstuffs such as pig and cattle. The analysis of real feedingstuffs containing macrolides demonstrated the fitness for purpose of the whole analytical procedure as well as a good fitting between real and spiked samples. The proposed methods appeared therefore as a sound alternative in the frame of control (e.g. for post-screening purposes) and/or monitoring surveillance programmes at the target level of 1.0 mg kg(-1) established according to the reported lowest dosage of additive needed to lead a growth promoting effect.

Repromicin derivatives with potent antibacterial activity against Pasteurella multocida.

Reductive amination of repromicin with polyfunctional amines has led to new macrolide antibacterial agents, some of which are highly potent against the Gram-negative pathogen Pasteurella multocida both in vitro and in a mouse infection model. A key element in this discovery was the recognition that among certain known macrolides increasing lipophilicity results in diminished in vivo activity. One repromicin derivative, 20-[N-[3-(dimethylamino)-propyl]-N-L-alanylamino]-20-deoxorepro micin (35), was selected for advanced evaluation. At 5 mg/kg, a single subcutaneous dose was found to control induced pasteurellosis in swine and induced respiratory disease in cattle.

New analogues of rosaramicin isolated from a Micromonospora strain. I. Taxonomy, fermentation, isolation and physico-chemical and biological properties.

Antibiotics 6108 A1, B, C and D, a new series of analogues of rosaramicin, were found together with rosaramicin, juvenimicin A4 and M-4365 A1 from the cultured broth of strain BA06108 which was assigned to be a new species of Micromonospora. 6108 A1 and C showed inhibitory activity against Gram-positive and some Gram-negative bacteria as potent as rosaramicin and exhibited low acute toxicity in mice. However, 6108 B showed less potent antimicrobial activity and 6108 D showed higher toxicity than those two antibiotics.

New cirramycin-family antibiotics F-1 and F-2. Selection of producer mutants, fermentation, isolation, structural elucidation and antibacterial activity.

Two new 16-membered macrolides, cirramycins F-1 and F-2, were isolated from the culture filtrate of a mutant strain B-1425 of Streptomyces cirratus JTB-3. The antibiotics were also produced by bio-transformation of cirramycin A1 using a blocked mutant strain A-0033. Structures of F-1 and F-2 have been elucidated by spectral interpretation and analysis of acid degradation products. Both involved isomeric modification of a neutral sugar; F-1 contained L-rhodinose, and F-2 L-amicetose. Based on spectral data, cirramycin F-1 and antibiotic A6888C were found to be identical. Cirramycins F-1 and F-2 are active against Gram-positive bacteria, but less active than cirramycin A1.

Carbomycin, a macrolide antibiotic.

Carbomycin is produced by Streptomyces halstedii. It was produced in a medium containing the following ingredients (g/l): soybean meal, 30.0; glucose, 22.0; NaCl, 1.0; CaCO3, 5.0; CoCl2 . 6 H2O, 0.005; and lard oil, 4.0. Influence of trace elements on the biosynthesis of carbomycin was recorded. Methods of extraction and purification were given in the review article. Chemical and physical properties of carbomycin were also described. A microbiological assay method for carbomycin determination was described. Biosynthesis of carbomycin was reported. Mechanism of action of carbomycin on micro-organisms was also given in the review article.

Analytical studies of maridomycin. II. Separation of 9-propionylmaridomycins by thin-layer chromatography.

Priopionyl derivatives of maridomycins, 9-propionylmaridomycins (PMDMs), are sixteen-membered ring macrolide antibiotics of six analogous components: I, II, III, IV, V and VI. The present paper deals with the separation and quantitative analysis of these components. The analysis was performed by thin-layer chromatographic separation, addition reaction of gaseous iodine with PMDMs on the plate, extraction of the PMDM-iodine complexes, and subsequent analysis of the amount of reacted iodine, using an automatic analysis system. To ascertain the reaction product of this system, PMDM III-iodine complex was synthesized separately under a liquid-phase reaction and the ratio of PMDM III and iodine atoms was determined to be 1:3 on physicochemical examination.

Analytical studies of maridomycin. I. High-performance liquid chromatography of marido-mycins and some other macrolide antibiotics.

Maridomycins and their acyl derivatives (9-propionyl, 2'-propionyl and 9,2'-dipropionyl maridomycins) were separated quantitatively into six components by high-performance liquid chromatography using a Corasil I column (200 cm X 2 mm I.D.) with a mixed sovent (upper layer of n-hexane, diisopropyl ether, ethanol and water) as the eluent. A linear relationship was found between the logarithm of the capacity factors (k') and the logarithm of the alkyl carbon numbers in the acyl group at position 4''. This relationship led to the discovery of a new component of maridomycin (3-propionyl-4''-n-butyryl analogue) in a crude sample. A similar relationship was found on chromatographic separation of some other macrolide antibiotics such as leucomycin, carbomycin A and B groups, under similar conditions.

Deltamycins, new macrolide antibiotics. II. Isolation and physicochemical properties.

The new macrolide antibiotics were isolated by silica gel chromatography. They showed a UV absorption maximum at 240 nm. Deltamycins A1, A2 and A3 were demonstrated to be new macrolide antibiotics on the basis of their physicochemical properties whereas deltamycin A4 was identified as carbomycin A.