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Journal ArticleDOI

Enhanced camptothecin production by ethanol addition in the suspension culture of the endophyte, Fusarium solani

01 Jul 2015-Bioresource Technology (Bioresour Technol)-Vol. 188, pp 251-257
TL;DR: The study indicates a dual role of ethanol, presumably as an elicitor and also as a carbon/energy source, leading to enhanced biomass and camptothecin production.
About: This article is published in Bioresource Technology.The article was published on 2015-07-01. It has received 48 citations till now. The article focuses on the topics: Fusarium solani & Energy source.
Citations
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Journal ArticleDOI
TL;DR: The effort has shifted towards optimizing culture conditions for high-value pharmaceuticals production through the application of cell line selection, elicitation, precursor feeding, two-phase co-culture among cell, tissue, and organ culture approaches.
Abstract: Biotechnology is playing a vital alternative role in the production of pharmaceutical plant secondary metabolites to support industrial production and mitigate over-exploitation of natural sources. High-value pharmaceuticals that include alkaloids, flavonoids, terpenes, steroids, among others, are biosynthesized as a defensive strategy by plants in response to perturbations under natural environmental conditions. However, they can also be produced using plant cell, tissue, and organ culture techniques through the application of various in vitro approaches and strategies. In the past decades, efforts were on the clonal propagation, biomass and secondary metabolites production in the in vitro cultures of medicinally important plants that produce these molecules. In recent years, the effort has shifted towards optimizing culture conditions for their production through the application of cell line selection, elicitation, precursor feeding, two-phase co-culture among cell, tissue, and organ culture approaches. The efforts are made with the possibility to scale-up the production, meet pharmaceutical industry demand and conserve natural sources of the molecules. Applications of metabolic engineering and production from endophytes are also getting increasing attention but, the approaches are far from practical application in their industrial production.

167 citations


Cites background from "Enhanced camptothecin production by..."

  • ...Addition of pure and ethanolic extract to the cultures of F. solani enhanced CPT production by 15.5 and 10.6-fold respectively (Venugopalan and Srivastava 2015)....

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Journal ArticleDOI
TL;DR: Various bioprocess optimization strategies that have been applied to sustain and enhance the product yield from the endophytes have been described in detail and techniques like mixed fermentation/co-cultivation and use of epigenetic modifiers have also been discussed as potential strategies to activate cryptic gene clusters in endophytic fungi, thereby aiding in novel metabolite discovery and overcoming the limitations associated with axenic culture.

164 citations

Journal ArticleDOI
TL;DR: Following the path traced by the blockbuster drug taxol, an increasing number of valuable compounds originally characterized as secondary metabolites of plant species belonging to the Spermatophyta have been reported as fermentation products of endophytic fungal strains.
Abstract: It is known that plant-based ethnomedicine represented the foundation of modern pharmacology and that many pharmaceuticals are derived from compounds occurring in plant extracts. This track still stimulates a worldwide investigational activity aimed at identifying novel bioactive products of plant origin. However, the discovery that endophytic fungi are able to produce many plant-derived drugs has disclosed new horizons for their availability and production on a large scale by the pharmaceutical industry. In fact, following the path traced by the blockbuster drug taxol, an increasing number of valuable compounds originally characterized as secondary metabolites of plant species belonging to the Spermatophyta have been reported as fermentation products of endophytic fungal strains. Aspects concerning sources and bioactive properties of these compounds are reviewed in this paper.

107 citations


Cites background from "Enhanced camptothecin production by..."

  • ...roseus containing strictosidine as a precursor in CPT biosynthesis, and even by ethanol itself [287]....

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Journal ArticleDOI
TL;DR: The results obtained in the present investigation suggest the use of elicitation as a promising alternative method to increase CPT production and cell growth in the cell suspension cultures of O. mungos.
Abstract: Production of camptothecin (CPT), an anticancer compound was enhanced in the cell suspension cultures of Ophiorrhiza mungos Linn. through elicitor treatment. Cell suspension culture was established using the friable callus tissues induced from the field grown leaf explants cultured in MS solid media supplemented with 3 % sucrose, 3 mg L−1 1-Naphthaleneacetic acid (NAA), 1 mg L−1 2,4-Dichlorophenoxyacetic acid (2,4-D) and 0.5 mg L−1 kinetin (KIN). The callus tissues were used for establishing cell suspension culture in half-strength MS (1/2X MS) liquid media supplemented with the same hormone concentration. NAA was found to be essential for the prolific growth of O. mungos cells in suspension culture. Influence of different elicitors such as yeast extract (YE) and silver nitrate (AgNO3) on cell growth, CPT accumulation and cell viability was studied and found that YE and AgNO3 caused a significant increase in biomass and CPT yield according to their concentration, incubation time and feeding time. A maximum of 13.3-fold increment in CPT production and threefold increase in cell growth were recorded in cell cultures elicited with 50 mg L−1 YE on the 10th day of incubation. Cell growth and CPT level were found to decrease in the cultures treated with high concentration of elicitors. CPT was estimated using high performance liquid chromatography (HPLC). The results obtained in the present investigation suggest the use of elicitation as a promising alternative method to increase CPT production and cell growth in the cell suspension cultures of O. mungos.

61 citations


Cites background from "Enhanced camptothecin production by..."

  • ...5-fold increase in CPT production was reported in the suspension culture of a CPT producing endophyte, Fusarium solani, using ethanol as an elicitor (Venugopalan and Srivastava 2015)....

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  • ...A 15.5-fold increase in CPT production was reported in the suspension culture of a CPT producing endophyte, Fusarium solani, using ethanol as an elicitor (Venugopalan and Srivastava 2015)....

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Journal ArticleDOI
TL;DR: The endophytic fungi from camptotheca trees are a reliable source for natural anticancer compounds and the fungal CPT exhibited effective activity at inhibiting cell growth and inducing apoptosis on Vero cells.
Abstract: Background: Camptothecin (CPT) is a potent drug against cancers, originally from plants. The endophytic fungi could produce the secondary metabolite same as the host and is used as medicine. Objectives: The aim of this paper was to investigate an endophytic fungal CPT with anti-neoplastic activity. Methods: Endophytic fungi were isolated from Camptotheca acuminata in China. CPT from strain S-019 was characterized by TLC, HPLC and EI-MS analysis. Anti-tumor activity of fungal CPT was detected by MTT and fluorescent dye methods using Vero and PC-3 cells. Results: A total of 94 endophytic fungi strains were isolated from tissues of C. acuminata and 16 fungi strains displayed cytotoxic activity on Vero or PC3 cells. Of which, the fungal strain S-019, classified as Fusarium solani , displayed impressive cytotoxic activity on cancer cells and was found to produce CPT by analysis of TLC, HPLC and EI-MS methods. Bioassay studies confirmed that the fungi CPT had potent cytotoxicity on Vero cells and induced apoptosis of Vero cells. Conclusion: The endophytic fungi from camptotheca trees are a reliable source for natural anticancer compounds. The endophytic fungi could produce CPT same as plant. The fungal CPT exhibited effective activity at inhibiting cell growth and inducing apoptosis on Vero cells. Keywords: Endophytic fungi, camptothecin, anti-tumor, Camptotheca acuminate

60 citations

References
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Journal ArticleDOI
TL;DR: The DNA-based methods that are available to detect/quantify spoilage bacteria, and relevant metabolic pathways in cheeses are reviewed and it is highlighted how these strategies can be employed to improve cheese quality and reduce the associated economic burden on cheese processors.
Abstract: The microbial profile of cheese is a primary determinant of cheese quality. Microorganisms can contribute to aroma and taste defects, form biogenic amines, cause gas and secondary fermentation defects, and can contribute to cheese pinking and mineral deposition issues. These defects may be as a result of seasonality and the variability in the composition of the milk supplied, variations in cheese processing parameters, as well as the nature and number of the non-starter microorganisms which come from the milk or other environmental sources. Such defects can be responsible for production and product recall costs and thus represent a significant economic burden for the dairy industry worldwide. Traditional non-molecular approaches are often considered biased and have inherently slow turnaround times. Molecular techniques can provide early and rapid detection of defects that result from the presence of specific spoilage microbes and, ultimately, assist in enhancing cheese quality and reducing costs. Here we review the DNA-based methods that are available to detect/quantify spoilage bacteria, and relevant metabolic pathways in cheeses and, in the process, highlight how these strategies can be employed to improve cheese quality and reduce the associated economic burden on cheese processors.

1,437 citations

Journal ArticleDOI
TL;DR: Despite the availability of only a limited number of biosynthetic genes, the research on C. roseus has already led to a broad scientific spin-off and it is clear that many interesting results can be expected when more genes become available.
Abstract: The Catharanthus (or Vinca) alkaloids comprise a group of about 130 terpenoid indole alkaloids. Vinblastine is now marketed for more than 40 years as an anticancer drug and became a true lead compound for drug development. Due to the pharmaceutical importance and the low content in the plant of vinblastine and the related alkaloid vincristine, Catharanthus roseus became one of the best-studied medicinal plants. Consequently it developed as a model system for biotechnological studies on plant secondary metabolism. The aim of this review is to acquaint a broader audience with the recent progress in this research and with its exciting perspectives. The pharmacognostical aspects of the Catharanthus alkaloids cover botanical (including some historical), phytochemical and analytical data. An up-to-date view on the biosynthesis of the alkaloids is given. The pharmacological aspects of these alkaloids and their semi-synthetic derivatives are only discussed briefly. The biotechnological part focuses on alternative production systems for these alkaloids, for example by in vitro culture of C. roseus cells. Subsequently it will be discussed to what extent the alkaloid biosynthetic pathway can be manipulated genetically ("metabolic engineering"), aiming at higher production levels of the alkaloids. Another approach is to produce the alkaloids (or their precursors) in other organisms such as yeast. Despite the availability of only a limited number of biosynthetic genes, the research on C. roseus has already led to a broad scientific spin-off. It is clear that many interesting results can be expected when more genes become available.

645 citations


"Enhanced camptothecin production by..." refers background in this paper

  • ...The plant is an ornamental shrub which grows like a weed in the tropics and is the source of about 130 different monoterpene indole alkaloids (but not CPT), all of which use strictosidine as a precursor (van Der Heijden et al., 2004)....

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Journal ArticleDOI
TL;DR: Isolation of an organism producing camptothecin and its fermentation may, in the future, provide an easily accessible source for the production of this anticancer drug precursor molecule.
Abstract: A fungal endophytic isolate, camptothecin, has been isolated from the inner bark of the plant Nothapodytes foetida from the Western coast of India. The fungus, which belongs to the family Phycomycetes, produced the anticancer drug lead compound camptothecin (1) when grown in a synthetic liquid medium (Sabouraud broth) under shake flask and bench scale fermentation conditions. Compound 1 was identified by means of chromatographic and spectroscopic methods. It was also compared with an authentic example for its biological activity against a number of human cancer cell lines. Isolation of an organism producing 1 and its fermentation may, in the future, provide an easily accessible source for the production of this anticancer drug precursor molecule.

383 citations


"Enhanced camptothecin production by..." refers methods in this paper

  • ...For extraction of CPT from the biomass, a protocol reported by Puri et al. (2005) was adopted for the study....

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  • ...The amount of CPT present in the sample was estimated on a high performance liquid chromatography instrument (Shimadzu Corporation, Japan) using the protocol suggested by Puri et al. (2005)....

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Journal ArticleDOI
TL;DR: The results offer a caution as to the possibility of using endophytic fungi as alternate sources of plant secondary metabolite production, and further studies have been initiated on the analysis of the upstream metabolic intermediates to understand the steps at which the production of the metabolites in question is constrained.
Abstract: The pentacyclic quinoline alkaloid camptothecin (1) is a potent antineoplastic agent. Two of its analogues, 9-methoxycamptothecin (2) and 10-hydroxycamptothecin (3), exhibit similar potency but do not have the potential therapeutic drawbacks produced by unmodified 1. We have established methodology for the isolation and unequivocal identification and characterization of a novel endophytic fungus isolated from the inner bark of the medicinal plant Camptotheca acuminata, which produced 1-3 in rich mycological medium (Sabouraud dextrose broth), under shake-flask fermentation conditions. The fungus was identified by its morphology and authenticated by ITS analysis (ITS1 and ITS2 regions and the intervening 5.8S rDNA region). Camptothecin (1) and its analogues were identified by 1H NMR spectroscopy and LC-HRMS and confirmed by comparison with authentic standards. The production pattern of the metabolites over seven successive subculture generations of this endophyte was studied. A sharp attenuation in the production of 1 and 2 was observed from the first- through to the seventh-generation subculture. Therefore, these results offer a caution as to the possibility of using endophytic fungi as alternate sources of plant secondary metabolite production. Further studies have been initiated on the analysis of the upstream metabolic intermediates to understand the steps at which the production of the metabolites in question is constrained.

346 citations

Journal ArticleDOI
TL;DR: Endophytic fungi strains from Apodytes dimidiata (Icacinaceae), a medium sized tree from the Western Ghats, India are isolated and identified as Fusarium solani using both ITS rDNA sequencing and spore morphology, both of which produced camptothecin and 9-methoxycamPTothecin in their mycelia.

254 citations


"Enhanced camptothecin production by..." refers background in this paper

  • ...The endophytic fungal strain used in the present study was, F. solani MTCC 9668 (Shweta et al., 2010), procured from Microbial Type Culture Collection and GenBank, Chandigarh, India....

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  • ...It is a highly effective anti-cancer molecule as it acts by binding to the topoisomerase I-DNA complex in cancer cells, thus preventing DNA replication and triggering cell death (Shweta et al., 2010)....

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