Getting to the bottom of Taxol biosynthesis by fungi

  title={Getting to the bottom of Taxol biosynthesis by fungi},
  author={Uwe Heinig and Susanne Scholz and Stefan Jennewein},
  journal={Fungal Diversity},
Taxol (paclitaxel) is a highly-oxygenated diterpenoid natural product first isolated from the pacific yew tree (Taxus brevifolia). It is one of the most widely used anticancer drugs. Soon after the discovery of its unique mode of action and the resulting high demand, an extensive search was initiated for alternative sources to replace the slow-growing and scarce pacific yew. Thus far, however, Taxol and related compounds have only been found in the genus Taxus, which comprises a small number of… 
Natural Sources of Taxol
Application of biotechnology through metabolic engineering is hoped to address the supply of taxol to meet demand for the production of the anticancer drug, considering the increasing prevalence of cancer around the world.
Conjugation of Aspergillus flavipes Taxol with Porphyrin Increases the Anticancer Activity of Taxol and Ameliorates Its Cytotoxic Effects
To increase the Taxol solubility and to reduce its cytotoxicity, Taxol was modified via chemical conjugation with porphyrin, and the degree of conjugations was checked from the Thin layer chromatography and UV spectral analysis.
Advances in exploring alternative Taxol sources
The advances in exploring alternative Taxol sources aside from total synthesis are introduced, including Taxol from nursery cultivated Taxus, semi-synthesis of Taxol, taxol from Taxus cell culture, production of taxol by synthetic biology, TaxolFrom the endophytic fungi and Taxolfrom other non-Taxus plants.
Exploiting the Biosynthetic Potency of Taxol from Fungal Endophytes of Conifers Plants; Genome Mining and Metabolic Manipulation
The objectives of this review were to nominate the endophytic fungal isolates with the Taxol producing potency from Taxaceae and Podocarpaceae, and emphasize the different approaches such as molecular manipulation, cultural optimization, co-cultivation for enhancing the taxol productivities.
Comparative transcriptome analysis of a taxol-producing endophytic fungus, Aspergillus aculeatinus Tax-6, and its mutant strain
The transcriptome of an endophytic fungus, Aspergillus aculeatinus Tax-6, was analyzed in order to understand the molecular mechanisms of producing fungal taxol and the potential for the construction of taxol-producing genetic engineering strains.
Taxol Origins and Production Development 2 . 1 Natural Role and Therapeutic Utilization
This chapter focuses on the currently utilized and emerging biosynthetic options for Taxol production and a particular emphasis is placed on the biosynthesis production hosts including macroscopic and unicellular plant species and more recent attempts to elucidate, transfer, and reconstitute the Taxol pathway within technically advanced microbial hosts.
Taxol from Corylus avellana: paving the way for a new source of this anti-cancer drug
A review of the literature suggests that C. avellana may act as a commercial and alternative source for taxol production in an eco-friendly way, which will meet the ever-increasing demand, and also help reducing the cost of this anti-cancer compound.


Taxol: A complex diterpenoid natural product with an evolutionarily obscure origin
Many genes and enzymes in the Taxus pathway for taxoid biosynthesis have now been identified, although gaps remain and it may be possible to improve taxoid synthesis through the genetic modification of Taxus cell cultures, by culturing endophytic fungi or by transferring the entire pathway into a heterologous expression host, such as Saccharomyces cerevisiae.
Taxomyces andreanae: a presumed paclitaxel producer demystified?
An in-depth investigation of Taxomyces andreanae - the very first presumed endophytic synthesizer of the diterpenoid, confirms the molecular blueprint for paclitaxel biosynthesis to be an inherent genetic trait of the endophyte and postulates that proclaiming the strain "a fungus factory for Taxol" might have been premature.
Taxol Biosynthesis and Molecular Genetics
Taxus suspension cells (induced for taxoid biosynthesis by methyl jasmonate) were used for feeding studies, as the foundation for cell-free enzymology and as the source of transcripts for cDNA library construction and a variety of cloning strategies.
An Endophytic Taxol-Producing Fungus from Taxus media, Cladosporium cladosporioides MD2
Fermentation processes using taxol-producing fungi other than Taxus spp. may be an alternative way to produce taxol, which is an important antitumor agent used widely in the clinic setting. In this
Taxol-producing [corrected] fungal endophyte, Pestalotiopsis species isolated from Taxus cuspidata.
Taxus spp. needles contain amounts of taxol comparable to the bark of Taxus brevifolia: analysis and isolation.
Taxus needles may provide a renewable source of this valuable compound taxol and 10-deacetylbaccatin III, a related compound that can be converted to taxol through a semi-synthetic route.
Cytochrome P450 oxygenases of Taxol biosynthesis
A combination of classical biochemical and molecular methods, including cell-free enzyme studies and differential-display of mRNA-reverse transcription polymerase chain reaction (RT-PCR) combined with a homology-based searching and random sequencing of a cDNA library from induced T. cuspidata cells, led to the discovery of six novel cytochrome P450 taxoid (taxane diterpenoid) hydroxylases.
Endophytic fungi: novel sources of anticancer lead molecules
The relationship between the plants and endophytes during the accumulation of these secondary metabolites is studied to provide alternative methods of natural product drug discovery which could be reliable, economical, and environmentally safe.
A new endophytic taxane production fungus from Taxus chinensis
More than 50 kinds of endophytic fungi associated with Taxus chinensis were isolated and examined as a potential source of the imposing anticancer drug taxol. Of these, four isolates show ability to
Taxol biosynthesis: Taxane 13α-hydroxylase is a cytochrome P450-dependent monooxygenase
A PCR-based differential display-cloning approach yielded a family of related cytochrome P450 genes, one of which was assigned as a taxane 10β-hydroxylase by functional expression in yeast and validates this strategy for elucidating the oxygenation steps of taxane diterpenoid (taxoid) metabolism.