Production of camptothecine using whey by an endophytic fungus: standardization using response surface methodology

Bhalkar, Bhumika N.; Bedekar, Priyanka A.; Patil, Swapnil M.; Patil, Satish S.; Govindwar, Sanjay P.

doi:10.1039/c5ra12212k

Cited by 26 publications

(7 citation statements)

References 25 publications

(43 reference statements)

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“…These results, emphasizes the hypothesis of cultural communication and cross-talking of the CPT producing and non-CPT producing microbial endophytes, negating the dependence of the CPT expression on the plant host-derived chemical signals [ 8 , 10 , 27 ]. Similar metabolic paradigm was observed for biosynthesis of Taxol by A. terreus with addition of microbiome of P. gracilior [ 42 , 60 , 61 , 64 , 68 ], Pericornia sp. [ 31 ].…”

Section: Discussionsupporting

confidence: 56%

Production, bioprocessing and antiproliferative activity of camptothecin from Aspergillus terreus, endophyte of Cinnamomum camphora: restoring their biosynthesis by indigenous microbiome of C. camphora

Eldeghidy,

Abdel-Fattah,

El-Sayed

et al. 2023

Microb Cell Fact

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Fungal producing potency of camptothecin (CPT) raise the hope for their usage to be a platform for industrial production of CPT, nevertheless, attenuation of their productivity of CPT with the subculturing and preservation is the challenge. So, screening for novel endophytic fungal isolates with a reliable CPT-biosynthetic stability was the objective. Among the isolated endophytic fungi from the tested medicinal plants, Aspergillus terreus OQ642314.1, endophyte of Cinnamomum camphora, exhibits the highest yield of CPT (89.4 μg/l). From the NMR, FT-IR and LC–MS/MS analyses, the extracted CPT from A. terreus gave the same structure and molecular mass fragmentation pattern of authentic CPT (349 m/z). The putative CPT had a significant activity against MCF7 (0.27 µM) and HEPG-2 (0.8 µM), with a strong affinity to inhibits the human Topoisomerase 1 activity (IC50 0.362 μg/ml) as revealed from the Gel-based DNA relaxation assay. The purified CPT displayed a strong antimicrobial activity for various bacterial (E. coli and B. cereus) and fungal (A. flavus and A. parasiticus) isolates, ensuring the unique tertiary, and stereo-structure of A. terreus for penetrating the microbial cell walls and targeting the topoisomerase I. The higher dual activity of the purified CPT as antimicrobial and antitumor, emphasize their therapeutic efficiency, especially with growth of the opportunistic microorganisms due to the suppression of human immune system with the CPT uses in vivo. The putative CPT had an obvious activity against the tumor cell (MCF7) metastasis, and migration as revealed from the wound healing assay. The overall yield of A. terreus CPT was maximized with the Blackett-Burman design by twofolds increment (164.8 μg/l). The CPT yield by A. terreus was successively diminished with the multiple fungal subculturing, otherwise, the CPT productivity of A. terreus was restored, and increased over the zero culture upon coculturing with C. camphora microbiome (1.5% w/v), ensuring the restoring of CPT biosynthetic potency of A. terreus by the plant microbiome-derived chemical signals “microbial communication”. This is the first report exploring the feasibility of A. terreus “endophyte of C. camphora” to be a preliminary platform for commercial production of CPT with a reliable sustainability upon uses of indigenous C. camphora microbiome.

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Section: Discussionsupporting

confidence: 56%

Production, bioprocessing and antiproliferative activity of camptothecin from Aspergillus terreus, endophyte of Cinnamomum camphora: restoring their biosynthesis by indigenous microbiome of C. camphora

Eldeghidy,

Abdel-Fattah,

El-Sayed

et al. 2023

Microb Cell Fact

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“…By using the fungal endophyte Fusarium oxysporum Kolhapurensis, isolated from Nothapodytes nimmonia Mabb. Grahm, a known producing plant [61], levels in the optimized medium ranged from 283 mg • L −1 and decreased to 33 µg • L −1 by the 8th subculture. It is possible that the initial concentration might be the highest yet reported, however, information as to the provenance of the culture used was lacking, so the absolute effect of supplementation cannot be determined.…”

Section: Supplementation Studies With Camptothecinproducing Endophytesmentioning

confidence: 99%

“…It would be interesting to be able to perform a thorough fermentation program utilizing the reported camptothecin producers, but what is definitely of interest is that Bhalkar et al [61,62] used fungal spores to begin their fermentations, so there was no potential for carryover from the plant source in those experiments.…”

Section: Supplementation Studies With Camptothecinproducing Endophytesmentioning

confidence: 99%

Plant Endophytes and Epiphytes: Burgeoning Sources of Known and “Unknown” Cytotoxic and Antibiotic Agents?

Newman¹,

Cragg²

2020

Planta Med

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In the last 20 or so years, the influence of endophytes and, quite recently, epiphytes of plants upon the compounds found in those plants, which were usually assumed to be phytochemicals produced by the plant for a variety of reasons, often as a defense against predators, is becoming more evident, in particular in the case of antitumor agents originally isolated from plant sources, though antibiotic agents might also be found, particularly from epiphytes. In this review, we started with the first report in 1993 of a taxol-producing endophyte and then expanded the compounds discussed to include camptothecin, the vinca alkaloids, podophyllotoxin, and homoharringtonine from endophytic microbes and then the realization that maytansine is not a plant secondary metabolite at all, and that even such a well-studied plant such as Arabidopsis thaliana has a vast repertoire of potential bioactive agents in its leaf epiphytic bacteria. We have taken data from a variety of sources, including a reasonable history of these discoveries that were not given in recent papers by us, nor in other papers covering this topic. The sources included the Scopus database, but we also performed other searches using bibliographic tools, thus, the majority of the papers referenced are the originals, though we note some very recent papers that have built on previous results. We concluded with a discussion of the more modern techniques that can be utilized to “persuade” endophytes and epiphytes to switch on silent biosynthetic pathways and how current analytical techniques may aid in evaluating such programs. We also comment at times on some findings, particularly in the case of homoharringtonine, where there are repetitious data reports differing by a few years claiming the same endophyte as the producer.

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“…19 Quantication of the amount of CPT present in the samples was done using standard calibration curve obtained by HPLC analysis (DGU-20A 5R, Shimadzu, Japan).…”

Section: Extraction Detection and Analysis Of Cptmentioning

confidence: 99%

Solid state fermentation of soybean waste and an up-flow column bioreactor for continuous production of camptothecine by an endophytic fungus Fusarium oxysporum

et al. 2016

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The potential of an endophytic fungus Fusarium oxysporum (NCIM 1383) to produce the anti-cancer prodrug 'camptothecine (CPT)' by solid state fermentation (SSF) of agro-industrial by-products was investigated. Amongst the various substrates used under optimized SSF conditions, soybean meal was found to be the most efficient medium for optimum production of CPT by the fungus. The effect of the addition of different complex protein sources to the soybean meal substrate on productivity by the fungus was also studied. The CPT production was found to be increased by 46.87% after supplementation of "whey concentrate powder" as a complex protein source to the soybean meal. The optimized SSF conditions were used to develop a bench-scale, up flow bioreactor to check its applicability for continuous CPT production which could yield up to 128 mg l À1 CPT after 48 h of incubation. Whey, when used as a source of moisture in SSF, also was found to play a vital role in enhancing the CPT yield. Environmental parameters such as chemical oxygen demand (COD), biological oxygen demand (BOD), total dissolved solids (TDS), total soluble solids (TSS) and total protein content of whey effluent after fermentation were found to be reduced significantly highlighting the environmental applications of the process developed. The SSF methodology applied in the present study allows bioutilization of cheaper substrates; soybean meal and whey, by the endophytic fungus for production of valuable anti-cancer pro drug CPT.

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Production of camptothecine using whey by an endophytic fungus: standardization using response surface methodology

Cited by 26 publications

References 25 publications

Production, bioprocessing and antiproliferative activity of camptothecin from Aspergillus terreus, endophyte of Cinnamomum camphora: restoring their biosynthesis by indigenous microbiome of C. camphora

Production, bioprocessing and antiproliferative activity of camptothecin from Aspergillus terreus, endophyte of Cinnamomum camphora: restoring their biosynthesis by indigenous microbiome of C. camphora

Plant Endophytes and Epiphytes: Burgeoning Sources of Known and “Unknown” Cytotoxic and Antibiotic Agents?

Solid state fermentation of soybean waste and an up-flow column bioreactor for continuous production of camptothecine by an endophytic fungus Fusarium oxysporum

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