Plant endophytic fungi are an important and novel resource of natural bioactive compounds with their potential applications in agriculture, medicine and food industry In the past two decades, many valuable bioactive compounds with antimicrobial, insecticidal, cytotoxic, and anticancer activities have been successfully discovered from endophytic fungi During the long period of co-evolution, a friendly relationship was formed between each endophyte and its host plant Some endophytes have the ability to produce the same or similar bioactive compounds as those originated from their host plants This review mainly deals with the research progress on endophytic fungi for producing plant-derived bioactive compounds such as paclitaxel, podophyllotoxin, camptothecine, vinblastine, hypericin, and diosgenin The relations between endophytic fungi and their host plants, biological activities and action mechanisms of these compounds from endophytic fungi, some available strategies for efficiently promoting production of these bioactive compounds, as well as their potential applications in the future will also be discussed It is beneficial for us to better understand and take advantage of plant endophytic fungi

Plant-derived bioactive compounds produced by endophytic fungi.

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 slow-growing plants with a broad but generally isolated geographical distribution. In 1993, Stierle and colleagues reported the independent biosynthesis of Taxol in an endophytic fungus isolated from Taxus brevifolia, which resulted in more than 160 subsequent publications and patents addressing the biosynthesis of Taxol and related taxanes by microorganisms. The literature on fungal taxane synthesis contains numerous inconsistencies, prompting us to thoroughly re-examine Taxol biosynthesis in endophytic fungi associated with Taxus spp. Using a combination of phytochemistry, molecular biology and genome sequencing, we were unable to find any evidence for independent taxane biosynthesis in any of the endophytes, including the isolate described in the original publication (Taxomyces andreanae) and several more recent isolates from Taxus trees. Our findings therefore resolve a long-standing mystery concerning the evolution of a complex terpenoid biosynthetic pathway in two distantly-related organisms.

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Getting to the bottom of Taxol biosynthesis by fungi

In the urgent search for more effective ways to treat cancer, new extraction methods of taxol from endophytic fungus have demonstrated high potential in increasing the efficiency of taxol extraction for more efficient and sustainable production of taxol and cancer treatment products. This paper summarizes recent advances in taxol-producing endophytic fungi, both in China and abroad, in the following areas: isolation and identification of endophytic fungi types, extraction and detection methods of endophytic taxol in plants, and improved efficiency of the extraction process. With the advancement of science and technology, new techniques in biotechnology, such as fungal strain improvement and recombining technique and microbial fermentation engineering, have increased the extraction yield from taxol-producing fungi, thereby improved the overall efficiency of taxol production.

A review: recent advances and future prospects of taxol-producing endophytic fungi

Plant endophytic fungi are an important and novel resource of natural bioactive compounds with their potential applications in agriculture, medicine and food industry. In the past two decades, many valuable bioactive compounds with antimicrobial, insecticidal, cytotoxic and anticancer activities have been successfully discovered from the endophytic fungi. During the long period of co-evolution, a friendly relationship was formed between each endophyte and its host plant. Some endophytes have the ability to produce the same or similar bioactive compounds as those originated from their host plants. This chapter mainly reviewed the research progress on the endophytic fungi for producing plant-derived bioactive compounds such as paclitaxel, podophyllotoxin, camptothecine, vinblastine, hypericin and diosgenin etc. The relations between the endophytic fungi and their host plants, some available strategies for efficiently promoting production of these bioactive compounds, as well as their potential applications in the future are also discussed. It is beneficial for us to better understand and take advantage of plant endophytic fungi.

Endophytic fungi for producing bioactive compounds originally from their host plants

A critical review on exploiting the pharmaceutical potential of plant endophytic fungi.

Aims: To characterize and identify a new taxol-producing fungal strain HD86-9 isolated from Taxus cuspidata in China.



Methods and Results:  Taxol extracted from strain HD86-9 was identified by HPLC and MS analyses. Strain HD86-9 was cultured and its morphology and phenotypes were described. HD86-9 displayed morphology most similar to that of Aspergillus niger but presented differences in the shape and size of the conidia. The growth evaluation showed that the maximal tolerable temperature of the new strain was 43°C, higher than that of the model Aspergillus niger. The 18S rDNA and the internal transcribed spacer region including the 5·8S rDNA of HD86-9 were amplified by PCR; molecular analysis of these sequences revealed their high similarity of 98% to those of Aspergillus niger.



Conclusions:  The morphology and molecular analysis identified HD86-9 as a new variant of taxol-producing endophytic fungi, and it was named Aspergillus niger var. taxi D.P. Zhou, K. Zhao and W.X. Ping, var. nov.



Significance and Impact of the Study:  As the first report of a taxol-producing variant of Aspergillus niger species, this study offers important information and a new resource for the production of an important anticancer drug by endofungus fermentation.

https://sfamjournals.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2672.2009.04305.x

T. Gao

Papers

Aspergillus niger var. taxi, a new species variant of taxol-producing fungus isolated from Taxus cuspidata in China.