scholarly journals New Insights into cytotoxic metabolites produced by Streptomyces griseus isolate KJ623766: Large scale production, structure elucidation and biological activities

2019 ◽  
Author(s):  
Ahmed S. Abu Zaid ◽  
Ahmed E. Aleissawy ◽  
Khaled Aboshanab ◽  
Mahmoud A. Yassien ◽  
Nadia A. Hassouna

Abstract Natural products particularly microbial metabolites have been the mainstay of cancer chemotherapy and are likely to provide many of the lead structures and derivatives with new biological activities. In this research, the production of some potential cytotoxic metabolites from Streptomyces (S.) griseus isolate KJ623766 was carried out in 1 4 L laboratory fermenter under specified optimum conditions (28°C temperature, 200 RPM rotation speed, uncontrolled PH, 3 vvm aeration and 2 bar airflow pressure). Using 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium-bromide (MTT) assay, the cytotoxic activity of the ethyl acetate (1:1, v/v) extract of cell free culture supernatant (CFCS) against Caco2 and Hela cancer cell lines was determined with CD 50 of 14 µg/ml and 20 µg/ml, respectively. Bioassay guided fractionation of the ethyl acetate extract using different chromatographic techniques had led to the purification of the cytotoxic metabolites coded W1, R1 and R2 with reproducible amounts of 20, 5, and 1.5 mg/l, respectively. The structures of respective metabolites were determined using various spectroscopic analysis and identified as genistein, β-rhodomycinone and γ- rhodomycinone, respectively. Accordingly, S. griseus isolate KJ623766 can be used as a potential industrial strain for the large scale production of the isoflavonoid genistein, as well as for the production of β-and γ- rhodomycinone to be used for the construction of new derivatives with more potent cytotoxic activities of the anthracycline family. This is the first report about the production of the isoflavonoid genistein by S. griseus KJ623766.

2019 ◽  
Author(s):  
Ahmed S. Abu Zaid ◽  
Ahmed E. Aleissawy ◽  
Khaled Aboshanab ◽  
Mahmoud A. Yassien ◽  
Nadia A. Hassouna

Abstract Natural products particularly microbial metabolites have been the mainstay of cancer chemotherapy and are likely to provide many of the lead structures and derivatives with new biological activities. In this research, the production of some potential cytotoxic metabolites from Streptomyces (S.) griseus isolate KJ623766 was carried out in 14 L laboratory fermenter under specified optimum conditions (28°C temperature, 200 RPM rotation speed, uncontrolled PH, 3 vvm aeration and 2 bar airflow pressure). After 72 hrs of incubation, the cell free culture supernatant (CFCS) was collected and extracted using ethyl acetate (1:1, v/v) at pH 7.0. Using 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium-bromide (MTT) assay, the cytotoxic activity of the ethyl acetate extract against Caco2 and Hela cancer cell lines was determined with CD50 of 14 µg/ml and 20 µg/ml, respectively. Bioassay guided fractionation of the ethyl acetate extract using different chromatographic techniques had led to the purification of the cytotoxic metabolites coded W1, R1 and R2 with reproducible amounts of 20, 5, and 1.5 mg/l, respectively. The structures of respective metabolites were determined based on the mass, 1D and 2D NMR spectroscopic analysis and were identified as genistein, β-rhodomycinone and γ- rhodomycinone, respectively. Accordingly, S. griseus isolate KJ623766 can be used as a potential industrial strain for the commercial production of the isoflavonoid genistein, as well as for the production of β-and γ- rhodomycinone to be used for the construction of new derivatives with more potent cytotoxic activities of the anthracycline family. To the best of our knowledge, this is the first report about the production of the isoflavonoid genistein by S. griseus KJ623766.


Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 4009
Author(s):  
Ahmed S. Abu Zaid ◽  
Ahmed E. Aleissawy ◽  
Ibrahim S. Yahia ◽  
Mahmoud A. Yassien ◽  
Nadia A. Hassouna ◽  
...  

Background: This study aimed to produce, purify, structurally elucidate, and explore the biological activities of metabolites produced by Streptomyces (S.) griseus isolate KJ623766, a recovered soil bacterium previously screened in our lab that showed promising cytotoxic activities against various cancer cell lines. Methods: Production of cytotoxic metabolites from S. griseus isolate KJ623766 was carried out in a 14L laboratory fermenter under specified optimum conditions. Using a 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium-bromide assay, the cytotoxic activity of the ethyl acetate extract against Caco2 and Hela cancer cell lines was determined. Bioassay-guided fractionation of the ethyl acetate extract using different chromatographic techniques was used for cytotoxic metabolite purification. Chemical structures of the purified metabolites were identified using mass, 1D, and 2D NMR spectroscopic analysis. Results: Bioassay-guided fractionation of the ethyl acetate extract led to the purification of two cytotoxic metabolites, R1 and R2, of reproducible amounts of 5 and 1.5 mg/L, respectively. The structures of R1 and R2 metabolites were identified as β- and γ-rhodomycinone with CD50 of 6.3, 9.45, 64.8 and 9.11, 9.35, 67.3 µg/mL against Caco2, Hela and Vero cell lines, respectively. Values were comparable to those of the positive control doxorubicin. Conclusions: This is the first report about the production of β- and γ-rhodomycinone, two important scaffolds for synthesis of anticancer drugs, from S. griseus.


Marine Drugs ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. 241
Author(s):  
Shaden A. M. Khalifa ◽  
Eslam S. Shedid ◽  
Essa M. Saied ◽  
Amir Reza Jassbi ◽  
Fatemeh H. Jamebozorgi ◽  
...  

Cyanobacteria are photosynthetic prokaryotic organisms which represent a significant source of novel, bioactive, secondary metabolites, and they are also considered an abundant source of bioactive compounds/drugs, such as dolastatin, cryptophycin 1, curacin toyocamycin, phytoalexin, cyanovirin-N and phycocyanin. Some of these compounds have displayed promising results in successful Phase I, II, III and IV clinical trials. Additionally, the cyanobacterial compounds applied to medical research have demonstrated an exciting future with great potential to be developed into new medicines. Most of these compounds have exhibited strong pharmacological activities, including neurotoxicity, cytotoxicity and antiviral activity against HCMV, HSV-1, HHV-6 and HIV-1, so these metabolites could be promising candidates for COVID-19 treatment. Therefore, the effective large-scale production of natural marine products through synthesis is important for resolving the existing issues associated with chemical isolation, including small yields, and may be necessary to better investigate their biological activities. Herein, we highlight the total synthesized and stereochemical determinations of the cyanobacterial bioactive compounds. Furthermore, this review primarily focuses on the biotechnological applications of cyanobacteria, including applications as cosmetics, food supplements, and the nanobiotechnological applications of cyanobacterial bioactive compounds in potential medicinal applications for various human diseases are discussed.


2016 ◽  
Vol 88 (9) ◽  
pp. 865-872 ◽  
Author(s):  
Gregor Tegl ◽  
Christoph Öhlknecht ◽  
Robert Vielnascher ◽  
Paul Kosma ◽  
Andreas Hofinger-Horvath ◽  
...  

AbstractChito-oligosaccharides (COSs) are a substance class of high interest due to various beneficial bioactive properties. However, detailed mechanistic and application-related investigations are limited due to the poor availability of COSs with defined structural properties. Here, we present the large-scale production of COSs with defined degree of N-acetylation using a commercial cellulase preparation from Trichoderma longibrachiatum. The enzyme preparation was found to exclusively produce COSs lacking of acetyl groups while MS/MS analysis indicated a cellobiohydrolase to be the responsible for hydrolysis with the enzyme preparation. MS and NMR analysis proved the low content of acetyl groups in the COS mix and oligomers with a degree of polymerization (DP) of 2–6 were obtained. The low cost enzyme source was further exploited for large-scale production in a 20 g batch and resulted a COSs yield of 40%. An inexpensive enzyme source for the production of bioactive COSs was successfully implemented and thorough product analysis resulted in well-defined COSs. This strategy could improve the access to this substance class for a more detailed investigation of its various biological activities.


2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Chia-Chien Hsieh ◽  
Blanca Hernández-Ledesma ◽  
Samuel Fernández-Tomé ◽  
Valerie Weinborn ◽  
Daniela Barile ◽  
...  

Milk is the most complete food for mammals, as it supplies all the energy and nutrients needed for the proper growth and development of the neonate. Milk is a source of many bioactive components, which not only help meeting the nutritional requirements of the consumers, but also play a relevant role in preventing various disorders. Milk-derived proteins and peptides have the potential to act as coadjuvants in conventional therapies, addressing cardiovascular diseases, metabolic disorders, intestinal health, and chemopreventive properties. In addition to being a source of proteins and peptides, milk contains complex oligosaccharides that possess important functions related to the newborn’s development and health. Some of the health benefits attributed to milk oligosaccharides include prebiotic probifidogenic effects, antiadherence of pathogenic bacteria, and immunomodulation. This review focuses on recent findings demonstrating the biological activities of milk peptides, proteins, and oligosaccharides towards the prevention of diseases of the 21st century. Processing challenges hindering large-scale production and commercialization of those bioactive compounds have been also addressed.


2020 ◽  
Vol 10 (2) ◽  
pp. 95-108
Author(s):  
Khushbu Gupta ◽  
Tejpal Singh Chundawat

In recent time, green synthesis of Metal Nanoparticles (MNPs) is the latest developing technology and received exceptional interest because it is simple, eco-friendly, pollutant-free, nontoxic, and a low-cost approach. Green route of biogenic synthesis of metal nanoparticles via microbes (bacteria, fungi, virus, yeast, algae etc.) has the potential to deliver clean manufacturing technology. Fungi are in the great use for the synthesis of nanoparticles and are more advantageous as compared with other microorganisms in several ways. Fungi grow in the form of a group of mycelia, which helps them to withstand flow pressure and agitation and various other conditions to which microbes are subjected to in a bioreactor, used for large-scale production. This review has its major focus on fungus Fusarium oxysporum, which is capable of synthesizing a large number of different types of nanoparticles such as titanium, magnesium, platinum, silver, gold, zirconium, and strontium, titania and silica oxide and many more. Biogenically synthesized nanoparticles are characterized by different techniques and exhibited biological activity. The fungi with metabolic capabilities can effectively synthesize a large number of nanoparticles both extracellularly and intracellularly. The biologically synthesized nanoparticles have wide ranges of applications especially in agricultural and medicinal industries.


1993 ◽  
Vol 32 (1) ◽  
pp. 129-131
Author(s):  
Naureen Talha

The literature on female labour in Third World countries has become quite extensive. India, being comparatively more advanced industrially, and in view of its size and population, presents a pictures of multiplicity of problems which face the female labour market. However, the author has also included Mexico in this analytical study. It is interesting to see the characteristics of developing industrialisation in two different societies: the Indian society, which is conservative, and the Mexican society, which is progressive. In the first chapter of the book, the author explains that he is not concerned with the process of industrialisation and female labour employed at different levels of work, but that he is interested in forms of production and women's employment in large-scale production, petty commodity production, marginal small production, and self-employment in the informal sector. It is only by analysis of these forms that the picture of females having a lower status is understood in its social and political setting.


2018 ◽  
Vol 15 (4) ◽  
pp. 572-575 ◽  
Author(s):  
Ponnusamy Kannan ◽  
Samuel I.D. Presley ◽  
Pallikondaperumal Shanmugasundaram ◽  
Nagapillai Prakash ◽  
Deivanayagam Easwaramoorthy

Aim and Objective: Itopride is a prokinetic agent used for treating conditions like non-ulcer dyspepsia. Itopride is administered as its hydrochloride salt. Trimethobenzamide is used for treating nausea and vomiting and administered as its hydrochloride salt. The aim is to develop a novel and environmental friendly method for large-scale production of itopride and trimethobenzamide. Materials and Methods: Itopride and trimethobenzamide can be prepared from a common intermediate 4- (dimethylaminoethoxy) benzyl amine. The intermediate is prepared from one pot synthesis using Phyrdroxybenzaldehye and zinc dust and further reaction of the intermediate with substituted methoxy benzoic acid along with boric acid and PEG gives itopride and trimethobenzamide. Results: The intermediate 4-(dimethylaminoethoxy) benzylamine is prepared by treating p-hydroxybenzaldehyde and 2-dimethylaminoethyl chloride. The aldehyde formed is treated with hydroxylamine hydrochloride. The intermediate is confirmed by NMR and the purity is analysed by HPLC. Conclusion: Both itopride and trimethobenzamide were successfully synthesized by this method. The developed method is environmental friendly, economical for large-scale production with good yield and purity.


Energies ◽  
2021 ◽  
Vol 14 (7) ◽  
pp. 1940
Author(s):  
Muhammad Usman Naseer ◽  
Ants Kallaste ◽  
Bilal Asad ◽  
Toomas Vaimann ◽  
Anton Rassõlkin

This paper presents current research trends and prospects of utilizing additive manufacturing (AM) techniques to manufacture electrical machines. Modern-day machine applications require extraordinary performance parameters such as high power-density, integrated functionalities, improved thermal, mechanical & electromagnetic properties. AM offers a higher degree of design flexibility to achieve these performance parameters, which is impossible to realize through conventional manufacturing techniques. AM has a lot to offer in every aspect of machine fabrication, such that from size/weight reduction to the realization of complex geometric designs. However, some practical limitations of existing AM techniques restrict their utilization in large scale production industry. The introduction of three-dimensional asymmetry in machine design is an aspect that can be exploited most with the prevalent level of research in AM. In order to take one step further towards the enablement of large-scale production of AM-built electrical machines, this paper also discusses some machine types which can best utilize existing developments in the field of AM.


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