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Unearthing the fungal endophyte Aspergillus terreus for chemodiversity and medicinal prospects: a comprehensive review.

ABSTRACT: Aspergillus terreus microorganism represents a promising prospective source for drug discovery since it is rich in diverse kinds of bioactive secondary metabolites. It contributed to many biotechnological applications and its metabolites are used in the synthesis of certain pharmaceuticals and food products, in addition to its useful uses in fermentation processes. There are about 346 compounds identified from marine and terrestrial-derived A. terreus from 1987 until 2022, 172 compounds of them proved a vast array of bioactivity. This review aimed to create an up-to-date comprehensive literature data of A. terreus's secondary metabolites classes supported by its different bioactivity data to be a scientific record for the next work in drug discovery.

SUBMITTER: Amr K

PROVIDER: S-EPMC10040139 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Unearthing the fungal endophyte Aspergillus terreus for chemodiversity and medicinal prospects: a comprehensive review.

Amr Khadiga K Ibrahim Nehal N Elissawy Ahmed M AM Singab Abdel Nasser B ANB

Fungal biology and biotechnology 20230325 1

Aspergillus terreus microorganism represents a promising prospective source for drug discovery since it is rich in diverse kinds of bioactive secondary metabolites. It contributed to many biotechnological applications and its metabolites are used in the synthesis of certain pharmaceuticals and food products, in addition to its useful uses in fermentation processes. There are about 346 compounds identified from marine and terrestrial-derived A. terreus from 1987 until 2022, 172 compounds of them ...[more]

PMID: 36966331

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Project description:Attenuation of camptothecin (CPT) productivity by fungi with preservation and subculturing is the challenge that halts fungi to be an industrial platform of CPT production. Thus, screening for novel endophytic fungal isolates with metabolic stability for CPT production was the objective. Catharanthus roseus is one of the medicinal plants with diverse bioactive metabolites that could have a plethora of novel endophytes with unique metabolites. Among the endophytes of C. roseus, Aspergillus terreus EFBL-NV OR131583.1 had the most CPT producing potency (90.2 μg/l), the chemical identity of the putative CPT was verified by HPLC, FT-IR, NMR and LC-MS/MS. The putative A. terreus CPT had the same molecular mass (349 m/z), and molecular fragmentation patterns of the authentic one, as revealed from the MS/MS analyses. The purified CPT had a strong activity against MCF7 (5.27 μM) and UO-31 (2.2 μM), with a potential inhibition to Topo II (IC50 value 0.52 nM) than Topo 1 (IC50 value 6.9 nM). The CPT displayed a high wound healing activity to UO-31 cells, stopping their metastasis, matrix formation and cell immigration. The purified CPT had a potential inducing activity to the cellular apoptosis of UO-31 by ~ 17 folds, as well as, arresting their cellular division at the S-phase, compared to the control cells. Upon Plackett-Burman design, the yield of CPT by A. terreus was increased by ~ 2.6 folds, compared to control. The yield of CPT by A. terreus was sequentially suppressed with the fungal storage and subculturing, losing ~ 50% of their CPT productivity by 3rd month and 5th generation. However, the productivity of the attenuated A. terreus culture was completely restored by adding 1% surface sterilized leaves of C. roseus, and the CPT yield was increased over-the-first culture by ~ 3.2 folds (315.2 μg/l). The restoring of CPT productivity of A. terreus in response to indigenous microbiome of C. roseus, ensures the A. terreus-microbiome interactions, releasing a chemical signal that triggers the CPT productivity of A. terreus. This is the first reports exploring the potency of A. terreus, endophyte of C. roseus" to be a platform for industrial production of CPT, with an affordable sustainability with addition of C. roseus microbiome.

Project description:Endophytic mycopopulation isolated from India's Queen of herbs Tulsi (Ocimum sanctum) were explored and investigated for their diversity and antiphytopathogenic activity against widespread plant pathogens Botrytis cinerea, Sclerotinia sclerotiorum, Rhizoctonia solani and Fusarium oxysporum. 90 fungal isolates, representing 17 genera were recovered from 313 disease-free and surface sterilised plant segments (leaf and stem tissues) from three different geographic locations (Delhi, Hyderabad and Mukteshwar) during distinct sampling times in consequent years 2010 and 2011 in India. Fungal endophytes were subjected to molecular identification based on rDNA ITS sequence analysis. Plant pathogens such as F. verticillioides, B. maydis, C. coarctatum, R. bataticola, Hypoxylon sp., Diaporthe phaseolorum, Alternaria tenuissima and A. alternata have occurred as endophyte only during second sampling (second sampling in 2011) in the present study. Bi-plot generated by principal component analysis suggested tissue specificity of certain fungal endophytes. Dendrogram revealed species abundance as a function of mean temperature of the location at the time of sampling. Shannon diversity in the first collection is highest in Hyderabad leaf tissues (H' = 1.907) whereas in second collection it was highest from leaf tissues of Delhi (H' = 1.846). Mukteshwar (altitude: 7500 feet) reported least isolation rate in second collection. Nearly 23% of the total fungal isolates were considered as potent biocontrol agent. Hexane extract of M. phaseolina recovered from Hyderabad in first collection demonstrated highest activity against S. sclerotiorum with IC50 value of 0.38 mg/ml. Additionally, its components 2H-pyran-2-one, 5,6-dihydro-6-pentyl and palmitic acid, methyl ester as reported by GC-MS Chromatogram upon evaluation for their antiphytopathogenic activity exhibited IC50 value of 1.002 and 0.662 against respectively S. sclerotiorum indicating their significant role in antiphytopathogenic activity of hexane extract. The production of 2H-pyran-2-one, 5,6-dihydro-6-pentyl from M. phaseolina, an endophytic fungus is being reported for the first time.

Project description:The metabolic potency of fungi as camptothecin producer elevates their prospective use as an industrial platform for commercial production, however, the loss of camptothecin productivity by fungi with the storage and subculturing are the major obstacle. Thus, screening for endophytic fungal isolates inhabiting ethnopharmacological plants with an obvious metabolic stability and sustainability for camptothecin biosynthesis could be one of the most feasible paradigms. Aspergillus terreus ON908494.1, an endophyte of Cestrum parqui was morphologically and molecularly verified, displaying the most potent camptothecin biosynthetic potency. The chemical identity of A. terreus camptothecin was confirmed from the HPLC, FTIR and LC-MS/MS analyses, gave the same molecular structure and mass fragmentation patterns of authentic one. The purified putative camptothecin displayed a strong anticancer activity towards HepG-2 and MCF-7 with IC50 values 0.96 and 1.4 µM, respectively, with no toxicity to OEC normal cells. As well as, the purified camptothecin displayed a significant antifungal activity towards fungal human pathogen Candida albicans, Aspergillus flavus, and A. parasiticus, ensuring the unique structural activity relationships of A. terreus camptothecin, as a powerful dually active anticancer and antimicrobial agent. The camptothecin productivity of A. terreus was maximized by bioprocessing with Plackett-Burman design, with an overall 1.5 folds increment (170.5 µg/L), comparing to control culture. So, the optimal medium components for maximum yield of camptothecin by A. terreus was acid why (2.0 mL/L), Diaion HP20 (2.0 g/L), Amberlite XAD (2.0 g/L), dextrin (5.0 g/L), glucose (10.0 g/L), salicylic acid (2.0 g/L), serine (4.0 g/L), cysteine (4.0 g/L) and glutamate (10.0 g/L), at pH 6 for 15 days incubation. By the 5th generation of A. terreus, the camptothecin yield was reduced by 60%, comparing to zero culture. Interestingly, the productivity of camptothecin by A. terreus has been completely restored and over increased (210 µg/L), comparing to the 3rd generation A. terreus (90 µg/L) upon addition of methanolic extracts of Citrus limonum peels, revealing the presence of some chemical signals that triggers the camptothecin biosynthetic machinery. The feasibility of complete restoring of camptothecin biosynthetic-machinery of A. terreus for stable and sustainable production of camptothecin, pave the way for using this fungal isolate as new platform for scaling-up the camptothecin production.

Dataset Information

Unearthing the fungal endophyte Aspergillus terreus for chemodiversity and medicinal prospects: a comprehensive review.

Publications

Unearthing the fungal endophyte Aspergillus terreus for chemodiversity and medicinal prospects: a comprehensive review.

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