Production, bioprocess optimization and anticancer activity of Camptothecin from Aspergillus terreus and Aspergillus flavus, endophytes of Ficus elastica

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El-Sayed, Ashraf S.A.Enzymology and Fungal Biotechnology Lab, Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, Egypt (author)

Production, bioprocess optimization and anticancer activity of Camptothecin from Aspergillus terreus and Aspergillus flavus, endophytes of Ficus elastica

Article/chapterEnglish2021

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Elsevier,2021
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LIBRIS-ID:oai:DiVA.org:umu-184463
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-184463URI
https://doi.org/10.1016/j.procbio.2021.05.007DOI

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Language:English
Summary in:English

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Attenuating the biosynthetic potency of camptothecin producing fungi with the multiple subculturing and storage is the major challenge that limits the scaling-up of this approach. Thus, screening for novel fungal isolates with reliable metabolic stability and sustainability for camptothecin production is the objective of this work. Among the recovered isolates, Aspergillus terreus (320 μg/l) and A. flavus (290 μg/l) "endophytes of Ficus elastica" were the most potent camptothecin producing isolates. The chemical identity of extracted camptothecin was resolved from the HPLC, NMR, FTIR and LC–MS analyses, with a strong antiproliferative activity against MCF7 (0.18 μM), LS174 T, HCT29 (0.29−0.43 μM), HEPG-2 (0.73 μM) cell lines. The yield of camptothecin was decreased by about > 60 % by the 7th subculturing for both fungal isolates. Upon using Blackett-Burman design to optimize their nutritional requirements by the fungal isolates, their yield of camptothecin were increased by approximately 2 folds, revealing the essentiality of some carbon, nitrogen and growth elicitors for biosynthesis of camptothecin. Interestingly, the biosynthetic machinery of camptothecin by the 7th generation fungal isolates were completely restored upon addition of 1% surface sterilized leaves of F. elastica, while all the other experimented plant extracts did not display any effect on camptothecin production. So, chemicals signals derived from the plant /or its entire microbiome "microbial communication" triggering the expression of camptothecin biosynthetic gene cluster of these fungi, could be the most conceivable hypothesis explaining the attenuation and restoration processes of camptothecin biosynthesis by target the fungal isolates. This is the first report describing the feasibility of A. terreus and A. flavus "endophytes of F. elastica" for camptothecin production with reliable metabolic and sustainable biosynthetic potency upon addition of the plant host's entire microbiome, that could be a preliminary platform for scaling-up of camptothecin production.

Subject headings and genre

NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
Anticancer activity
Aspergillus terreus
Camptothecin
Endophytic fungi
Nutritional optimization

Added entries (persons, corporate bodies, meetings, titles ...)

Khalaf, Salwa A.Enzymology and Fungal Biotechnology Lab, Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, Egypt (author)
Azez, Hany A.Enzymology and Fungal Biotechnology Lab, Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, Egypt (author)
Hussein, Hussein A.Enzymology and Fungal Biotechnology Lab, Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, Egypt (author)
EL-Moslamy, Shahira H.Genetic Engineering and Biotechnology Research Institute (GEBRI), City of Scientific Research and Technology Applications, New Borg El-Arab City, Alexandria, Egypt (author)
Sitohy, BaselUmeå universitet,Onkologi,Klinisk immunologi(Swepub:umu)balsiy01 (author)
El-Baz, Ashraf F.Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat University City, Sadat City, Egypt (author)
Enzymology and Fungal Biotechnology Lab, Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, EgyptGenetic Engineering and Biotechnology Research Institute (GEBRI), City of Scientific Research and Technology Applications, New Borg El-Arab City, Alexandria, Egypt (creator_code:org_t)

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In:Process Biochemistry: Elsevier107, s. 59-731359-51131873-3298

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