Antitumor compounds from Streptomyces sp. KML-2, isolated from Khewra salt mines, Pakistan

BACKGROUND: Actinomycetes are gram positive bacteria with high G + C content in their DNA and are capable of producing variety of secondary metabolites. Many of these metabolites possess different biological activities and have the potential to be developed as therapeutic agents. The aim of the present study was to screen actinomycetes inhabiting halophilic environment such as Khewra salt mines present in Pakistan for cytotoxic and antitumor compounds. RESULTS: An actiomycetes strain designated as Streptomyces sp. KML-2 was isolated from a saline soil of Khewra salt mines, Pakistan. The strain Streptomyces sp. KML-2 showed 84 % cytotoxic activity against larvae of Artemiasalina. In the screening phase, the strain exhibited significant antitumor activity with IC50 values of 12, 48 and 56 µg/ml against Hela, MDBK and Vero cell lines, respectively. After that extract from 20 l fermentation was used to purify secondary metabolites by several chromatographic techniques. Structure elucidation of isolated compounds revealed that it is highly stable producer of Chromomycin SA (1) and 1-(1H-indol-3-yl)-propane-1,2,3-triol (2). Both of the isolated compounds showed significant antitumor activity against Hela and MCF-7 cancer cell lines (IC50 values 8.9 and 7.8 µg/ml against Hela; 12.6 and 0.97 µg/ml against MCF-7, respectively). The 16S rRNA gene sequence (1437 bp) of the strain confirm its identity (99 %) with Streptomyces griseus. CONCLUSIONS: From this research work we were successful in isolating two potent antitumor compounds, Chromomycin SA and 1-(1H-indol-3-yl)-propane-1,2,3-triol from Streptomyces KML-2 strain, isolated from Khewra salt mine. As such this is the second report which confirms that S. griseus can produce Chromomycin SA without introducing any mutagenesis in its biosynthesizing gene cluster and isolated indole derivative is being reported first time from any member of actinomycetes group with having novel antitumor activity against Hela and MCF-7 cells Nucleotide sequences: Nucleotide sequence data reported are available in the GenBank database under the accession number: GenBank KJ009562.

Heterologous expression and enzymatic analysis of Streptomyces griseus trypsin in Streptomyces lividans / 生物工程学报

Trypsin as an important serine protease has been widely used in food, pharmaceutical and tanning industries. In this study, we successfully expressed trypsin (cloning from Streptomyces griseus ATCC10137) in Streptomyces lividans TK24 and comparatively investigated its enzymatic properties. Specifically, applying S. griseus ATCC 10137 genome as template, we obtained the sprT gene and sub-cloned it into the expression plasmid pIJ86, generating the recombinant strain S. lividans TK24/pIJ86-sprT. When cultivated in R2YE and SELF, the activity of rSGT reached 9.21 U/mL and 8.61 U/mL, respectively. Meanwhile, the results of the enzymatic analysis showed that rSGT exhibited a higher acid tolerance and a higher specificity to hydrolyze amide bonds compared with bovine trypsin (BT). In addition, Zn2+ and organic solvents up-regulated esterase and amidase of rSGT. Taken together, the results obtained herein provide meaningful information for further modification of rSGT and its industrial application.

Oxidation of meloxicam by streptomyces griseus

The aim of the present investigation was to biotransform the anti-inflammatory compound meloxicam by enzymes present in whole cells of five actinomycete cultures to produce novel bioactive derivatives. Among the actinomycetes screened, Streptomyces griseus NCIM 2622 was found to possess the enzyme system[s] that oxidize meloxicam into two metabolites whereas that present in S. griseus NCIM 2623 could oxidize meloxicam to only one etabolite in significant quantities. The formation of enzymatic metabolites was monitored and confirmed by high-performance liquid chromatography [HPLC] analysis. The structures were elucidated based on liquid chromatography-tandem mass spectrometry [LC-MS/MS] data and previous reports as 5-hydroxymethyl meloxicam and 5-carboxy meloxicam. From the results obtained in this study, it can be concluded that S. griseus NCIM 2622 possesses oxidizing enzymes, which can be employed to oxidize meloxicam

Aminoglucósidos: mirada actual desde su historia / Aminoglucósidos: current look since its history

Se refiere la historia, mecanismos de acción y eficacia de los aminoglucósidos en los pacientes pediátricos, así como las limitaciones de su utilidad por el surgimiento de resistencias bacterianas originadas por empleo abusivo. Se presenta la estrategia de administración de monodosis, como alternativa frente al método tradicional de dosis fraccionadas, y también las complicaciones más frecuentes y graves de los aminoglucósidos y su sinergismo con otras familias de antimicrobianos. Y se citan investigaciones realizadas en el país en materia de terapia antibiótica.

We referred to history, mechanisms of action and efficacy of aminoglycosides in pediatric patients as well as limitations in their use because of the emergence of bacterial resistance caused by overuse. The one-dose administration strategy as an alternative to the traditional methods of fractioned doses, the most frequent and serious complictions of aminoglycosides and their sinergism with other antimicrobial families were presented. We quoted research studies on antibiotic therapy made in the country.

evaluation of the potent inhibitory effects of royal jelly fractions against streptomyces bacteria

To investigate the anti-bacterial properties of royal jelly against six different bacteria [Escherichia coil, Staphylococcus aureus, Streptomyces griseus, and three unclassified strains of Streptomyces]. Design: To find out the antibacterial properties of royal jelly by means of agar distribution method [drop-plate]. Setting: The diameter of the clean zone formed in each concentration was measured and correlated to the ability of the extracts to inhibit the growth of microorganisms. Interestingly the results show inhibitory effects of royal jelly on different strains of the bacteria in-vitro. Four concentrations of water soluble extracts of pure royal jelly were prepared and added drop wise to the bacterial strains seed layer cultured individually. Main outcome measures: Ether-soluble and non-soluble fractions of the royal jelly were also examined using the above method. It was found that the antibacterial effect of ether-soluble fraction is substantially higher than the effect of ether non-soluble fraction. The zones formed by ether-soluble fractions of royal jelly in the route of distribution in agar belong to the potency of anti-bacterial properties of fatty acids present in this fraction of royal jelly [10 -HDA]. Conclusions: The non ether-soluble fraction of royal jelly contains a bactericidal substance called royalisin that was found to have potent antibacterial activity. This fraction of royal jelly revealed weaker antibacterial effect than the ether-soluble fraction and even of pure royal jelly. Hence apart from its nutritional and medicinal effects, royal jelly's bactericidal ability should be considered and employed whenever appropriate in clinical medicine

Regulatory enzymes for the screening of streptomycin producing mutant strains of Streptomyces griseus.

Intermediary enzymes of streptomycin biosynthesis-arginine amidinotransferase and alkaline phosphatase were located at the early fermentation stages. Their relationship with streptomycin production by Streptomyces griseus strains GX-19 and MR-20 was determined and the use of this relationship was made for the screening of streptomycin producing mutant strains.

Selective strategies for antibiotic fermentation, Part II: Effect of aeration on streptomycin production by Streptomyces griseus JB-19.

The effect of higher aerated fermentation medium which enhanced streptomycin production by Streptomyces griseus JB-19 was found mainly related to the changes in dextrose consumption, inorganic phosphate utilisation and ammonia nitrogen accumulation under optimal and suboptimal supply of soluble vegetative protein.

Selective strategies for antibiotic fermentation. Part I.: The role of soluble vegetative protein in streptomycin production by Streptomyces griseus.

The soluble vegetative protein was found to enhance the production of streptomycin. It seems to be maintaining a balance between glucose consumption and phosphate utilization. Soluble vegetative protein was found to be the chief source of soluble inorganic phosphate, which when monitored along with dextrose addition boosted streptomycin production considerably.