Dataset Information

Hyper-production of taxol from Aspergillus fumigatus, an endophytic fungus isolated from Taxus sp. of the Northern Himalayan region.

ABSTRACT: Taxol® (generic name Paclitaxel) is a chemotherapeutic drug, effective against head, neck, breast, lung, bladder, ovary, and cervix cancers. Rising demands in chemotherapy and limited supply of natural taxol have ultimately increased the cost of the drug. Semi synthesis using taxol precursors is not able to meet the global supply and has intensified the need to find alternative ways of taxol production. In the present study, 34 different endophytes were isolated from Taxus sp. collected from Shimla, Himachal Pradesh (India). Primary screening of taxol-producing fungi was carried out based on the presence of dbat gene, essential for the taxol biosynthetic pathway. A fungal isolate TPF-06 was screened to be a taxol-producing strain based on the PCR amplification results. It was characterized and identified as Aspergillus fumigatus by 18S rRNA (Accession No. KU-837249). Multiple sequence alignment (MSA) of nuclear ribosomal internal transcribed spacer (ITS) region and phylogenetic analysis confirmed that strain belonged to A. fumigatus clade (Accession No. MF-374798) and is endophytic in nature. Presence of taxol was detected and quantified by High-Performance Liquid Chromatography (HPLC) and characterized by using Thin Layer Chromatography (TLC), Ultraviolet (UV) spectroscopy, Mass spectrometry (MS), Fourier-Transform Infrared Spectroscopy (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopy. Microbial fermentation in the S7 medium yielded 1.60?g/L of taxol, which to the best of our knowledge is the highest taxol production from an endophytic fungus. Findings of the present study suggest that the A. fumigatus is an excellent alternate source for taxol supply, and it may become a highly potent strain on a commercial scale. The involvement of dbat gene in A. fumigatus KU-837249 strain further suggested a way of increasing taxol yield in fungi by medium engineering and recombinant DNA technology in the future.

SUBMITTER: Kumar P

PROVIDER: S-EPMC6881681 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Hyper-production of taxol from Aspergillus fumigatus, an endophytic fungus isolated from Taxus sp. of the Northern Himalayan region.

Kumar Pradeep P Singh Balwant B Thakur Vikram V Thakur Abhishek A Thakur Nandita N Pandey Deepak D Chand Duni D

Biotechnology reports (Amsterdam, Netherlands) 20191115

Taxol® (generic name Paclitaxel) is a chemotherapeutic drug, effective against head, neck, breast, lung, bladder, ovary, and cervix cancers. Rising demands in chemotherapy and limited supply of natural taxol have ultimately increased the cost of the drug. Semi synthesis using taxol precursors is not able to meet the global supply and has intensified the need to find alternative ways of taxol production. In the present study, 34 different endophytes were isolated from Taxus sp. collected f ...[more]

PMID: 31799144

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Project description:BackgroundTaxol from Taxus species is a precious drug used for the treatment of cancer and can effectively inhibit the proliferation of cancer cells. However, the growth of Taxus plants is very slow and the content of taxol is quite low. Therefore, it is of great significance to improve the yield of taxol by modern biotechnology without destroying the wild forest resources. Endophytic fungus which symbiosis with their host plants can promote the growth and secondary metabolism of medicinal plants.ResultsHere, an endophytic fungus KL27 was isolated from T. chinensis, and identified as Pseudodidymocyrtis lobariellae. The fermentation broth of KL27 (KL27-FB) could significantly promote the accumulation of taxol in needles of T. chinensis, reaching 0.361 ± 0.082 mg/g·DW (dry weight) at 7 days after KL27-FB treatment, which is 3.26-fold increase as compared to the control. The RNA-seq and qRT-PCR showed that KL27-FB could significantly increase the expression of key genes involved in the upstream pathway of terpene synthesis (such as DXS and DXR) and those in the taxol biosynthesis pathway (such as GGPPS, TS, T5OH, TAT, T10OH, T14OH, T2OH, TBT, DBAT and PAM), especially at the early stage of the stimulation. Moreover, the activation of jasmonic acid (JA) biosynthesis and JA signal transduction, and its crosstalk with other hormones, such as gibberellin acid (GA), ethylene (ET) and salicylic acid (SA), explained the elevation of most of the differential expressed genes related to taxol biosynthesis pathway. Moreover, TF (transcriptional factor)-encoding genes, including MYBs, ethylene-responsive transcription factors (ERFs) and basic/helix-loop-helix (bHLH), were detected as differential expressed genes after KL27-FB treatment, further suggested that the regulation of hormone signaling on genes of taxol biosynthesis was mediated by TFs.ConclusionsOur results indicated that fermentation broth of endophytic fungus KL27-FB could effectively enhance the accumulation of taxol in T. chinensis needles by regulating the phytohormone metabolism and signal transduction and further up-regulating the expression of multiple key genes involved in taxol biosynthesis. This study provides new insight into the regulatory mechanism of how endophytic fungus promotes the production and accumulation of taxol in Taxus sp.

Dataset Information

Hyper-production of taxol from Aspergillus fumigatus, an endophytic fungus isolated from Taxus sp. of the Northern Himalayan region.

Publications

Hyper-production of taxol from <i>Aspergillus fumigatus</i>, an endophytic fungus isolated from <i>Taxus</i> sp. of the Northern Himalayan region.

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