Annulohypoxylon sp. strain MUS1, an endophytic fungus isolated from Taxus wallichiana Zucc., produces taxol and other bioactive metabolites

Gauchan, Dhurva Prasad; Vélëz, Heriberto; Acharya, Ashesh; Östman, Johnny R.; Lundén, Karl; Elfstrand, Malin; García‐Gil, Maria Rosario

doi:10.1007/s13205-021-02693-z

Cited by 11 publications

(8 citation statements)

References 39 publications

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“…), Vinblastine produced by Curvularia verruculosa, and Vincristine by Fusarium oxysporum isolated from Catharanthus roseus , Podophyllotoxin from Phialocephala fortinii , Camptothecin from Entrophospora infrequens from the plant Nothapodytes nimmoniana etc. [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

Integrated Machine Learning and Chemoinformatics-Based Screening of Mycotic Compounds against Kinesin Spindle ProteinEg5 for Lung Cancer Therapy

et al. 2022

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Among the various types of cancer, lung cancer is the second most-diagnosed cancer worldwide. The kinesin spindle protein, Eg5, is a vital protein behind bipolar mitotic spindle establishment and maintenance during mitosis. Eg5 has been reported to contribute to cancer cell migration and angiogenesis impairment and has no role in resting, non-dividing cells. Thus, it could be considered as a vital target against several cancers, such as renal cancer, lung cancer, urothelial carcinoma, prostate cancer, squamous cell carcinoma, etc. In recent years, fungal secondary metabolites from the Indian Himalayan Region (IHR) have been identified as an important lead source in the drug development pipeline. Therefore, the present study aims to identify potential mycotic secondary metabolites against the Eg5 protein by applying integrated machine learning, chemoinformatics based in silico-screening methods and molecular dynamic simulation targeting lung cancer. Initially, a library of 1830 mycotic secondary metabolites was screened by a predictive machine-learning model developed based on the random forest algorithm with high sensitivity (1) and an ROC area of 0.99. Further, 319 out of 1830 compounds screened with active potential by the model were evaluated for their drug-likeness properties by applying four filters simultaneously, viz., Lipinski’s rule, CMC-50 like rule, Veber rule, and Ghose filter. A total of 13 compounds passed from all the above filters were considered for molecular docking, functional group analysis, and cell line cytotoxicity prediction. Finally, four hit mycotic secondary metabolites found in fungi from the IHR were screened viz., (−)-Cochlactone-A, Phelligridin C, Sterenin E, and Cyathusal A. All compounds have efficient binding potential with Eg5, containing functional groups like aromatic rings, rings, carboxylic acid esters, and carbonyl and with cell line cytotoxicity against lung cancer cell lines, namely, MCF-7, NCI-H226, NCI-H522, A549, and NCI H187. Further, the molecular dynamics simulation study confirms the docked complex rigidity and stability by exploring root mean square deviations, root mean square fluctuations, and radius of gyration analysis from 100 ns simulation trajectories. The screened compounds could be used further to develop effective drugs against lung and other types of cancer.

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Section: Discussionmentioning

confidence: 99%

Integrated Machine Learning and Chemoinformatics-Based Screening of Mycotic Compounds against Kinesin Spindle ProteinEg5 for Lung Cancer Therapy

et al. 2022

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“…are many reports of fungi that can produce paclitaxel that were isolated as endophytes from plants that also produce paclitaxel and from plants that do not produce paclitaxel (e.g., Wollemia nobilis, Ginkgo biloba, and Corchorus olitorius L.) (Flores-Bustamante et al, 2010;Zhou et al, 2010;Hao et al, 2013;Gond et al, 2014;Kusari et al, 2014;Das et al, 2017). In Taxus spp., production of paclitaxel requires about 19 enzymatic steps, but very little is known about the biosynthetic machinery responsible for paclitaxel production in fungi (Gond et al, 2014;Kusari et al, 2014). In addition, paclitaxel has been shown to be produced by actinomycetes and, most recently, bacteria isolated from marine macroalgae; however, the biosynthetic pathway also remains elusive in these organisms (Caruso et al, 2000;Subramanian and Marudhamuthu, 2020).…”

Section: Figurementioning

confidence: 99%

“…Interestingly, fungi that have been isolated from Taxus spp. as endophytes known to produce paclitaxel (Flores-Bustamante et al, 2010;Zhou et al, 2010;Hao et al, 2013;Gond et al, 2014;Kusari et al, 2014) also cause diseases on Taxus spp. (Mirski, 2012).…”

Section: Figurementioning

confidence: 99%

“…Fungi used in this study were previously isolated from T. wallichiana [Table 1; (Gauchan et al, 2021)] and were maintained in malt extract agar (MEA; Duchefa Biochemie) at 20 • C. Solid Modified Melin Norkrans medium (MMN; Marx 1969) and potato dextrose agar (PDA; Thermo Fisher) were used for the growth assays. Liquid MMN media were used to grow the fungi for genomic DNA (gDNA) and RNA extraction.…”

Section: Strains and Mediamentioning

confidence: 99%

“…The anticancer compound, paclitaxel (Taxol R ; Figure 1), has been isolated from several plants, including yews (Taxus species), bald cypress (Taxodium distichum L.), plum-yew (Cephalotaxus mannii, C. fortunei, C. hainanensis), yew-pine (Podocarpus forrestii), and hazel (Corylus avellana L.) (Baloglu and Kingston, 1999;Zhou et al, 2010;Wang et al, 2011;Hao et al, 2013;Gond et al, 2014;Kusari et al, 2014). Likewise, there…”

Section: Introductionmentioning

confidence: 99%

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Taxol and β-tubulins from endophytic fungi isolated from the Himalayan Yew, Taxus wallichiana Zucc.

2022

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Paclitaxel, better known as the anticancer drug Taxol®, has been isolated from several plant species and has been shown to be produced by fungi, actinomycetes, and even bacteria isolated from marine macroalgae. Given its cytostatic effect, studies conducted in the 1990's showed that paclitaxel was toxic to many pathogenic fungi and oomycetes. Further studies led to the idea that the differences in paclitaxel sensitivity exhibited by different fungi were due to differences in the β-tubulin protein sequence. With the recent isolation of endophytic fungi from the leaves and bark of the Himalayan Yew, Taxus wallichiana Zucc., and the availability of genomes from paclitaxel-producing fungi, we decided to further explore the idea that endophytic fungi isolated from Yews should be well-adapted to their environment by encoding β-tubulin proteins that are insensitive to paclitaxel. Our results found evidence of episodic positive/diversifying selection at 10 sites (default p-value threshold of 0.1) in the β-tubulin sequences, corresponding to codon positions 33, 55, 172, 218, 279, 335, 359, 362, 379, and 406. Four of these positions (i.e., 172, 279, 359, and 362) have been implicated in the binding of paclitaxel by β-tubulin or formed part of the binding pocket. As expected, all the fungal endophytes grew in different media regardless of the paclitaxel concentration tested. Furthermore, our results also showed that Taxomyces andreanae CBS 279.92, the first fungus shown to produce paclitaxel, is a Basidiomycete fungus as the two beta tubulins encoded by the fungus clustered together with other Basidiomycete fungi.

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Vulnerability assessment of Taxus wallichiana in the Indian Himalayan Region to future climate change using species niche models and global climate models under future climate scenarios

Tiwary,

Singh,

Adhikari

et al. 2024

Biodivers Conserv

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Annulohypoxylon sp. strain MUS1, an endophytic fungus isolated from Taxus wallichiana Zucc., produces taxol and other bioactive metabolites

Cited by 11 publications

References 39 publications

Integrated Machine Learning and Chemoinformatics-Based Screening of Mycotic Compounds against Kinesin Spindle ProteinEg5 for Lung Cancer Therapy

Integrated Machine Learning and Chemoinformatics-Based Screening of Mycotic Compounds against Kinesin Spindle ProteinEg5 for Lung Cancer Therapy

Taxol and β-tubulins from endophytic fungi isolated from the Himalayan Yew, Taxus wallichiana Zucc.

Vulnerability assessment of Taxus wallichiana in the Indian Himalayan Region to future climate change using species niche models and global climate models under future climate scenarios

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