Endophytic fungi or endophytes exist widely inside the healthy tissues of living plants, and are important components of plant micro-ecosystems Over the long period of evolution, some co-existing endophytes and their host plants have established a special relationship with one and another, which can significantly influence the formation of metabolic products in plants, then affect quality and quantity of crude drugs derived from medicinal plants This paper will focus on the increasing knowledge of relationships between endophytic fungi and medicinal plants through reviewing of published research data obtained from the last 30 years The analytical results indicate that the distribution and population structure of endophytes can be considerably affected by factors, such as the genetic background, age, and environmental conditions of their hosts On the other hand, the endophytic fungi can also confer profound impacts on their host plants by enhancing their growth, increasing their fitness, strengthening their tolerances to abiotic and biotic stresses, and promoting their accumulation of secondary metabolites All the changes are very important for the production of bioactive components in their hosts Hence, it is essential to understand such relationships between endophytic fungi and their host medicinal plants Such knowledge can be well exploited and applied for the production of better and more drugs from medicinal plants

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A Friendly Relationship between Endophytic Fungi and Medicinal Plants: A Systematic Review.

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.

Cancer is a major killer disease all over the world and more than six million new cases are reported every year. Nature is an attractive source of new therapeutic compounds, as a tremendous chemical diversity is found in millions of species of plants, animals, and microorganisms. Plant-derived compounds have played an important role in the development of several clinically useful anti-cancer agents. These include vinblastine, vincristine, camptothecin, podophyllotoxin, and taxol. Production of a plant-based natural drug is always not up to the desired level. It is produced at a specific developmental stage or under specific environmental condition, stress, or nutrient availability; the plants may be very slow growing taking several years to attain a suitable growth phase for product accumulation and extraction. Considering the limitations associated with the productivity and vulnerability of plant species as sources of novel metabolites, microorganisms serve as the ultimate, readily renewable, and inexhaustible source of novel structures bearing pharmaceutical potential. Endophytes, the microorganisms that reside in the tissues of living plants, are relatively unstudied and offer potential sources of novel natural products for exploitation in medicine, agriculture and the pharmaceutical industry. They develop special mechanisms to penetrate inside the host tissue, residing in mutualistic association and their biotransformation abilities opens a new platform for synthesis of novel secondary metabolites. They produce metabolites to compete with the epiphytes and also with the plant pathogens to maintain a critical balance between fungal virulence and plant defense. It is therefore necessary that the relationship between the plants and endophytes during the accumulation of these secondary metabolites is studied. Insights from such research would provide alternative methods of natural product drug discovery which could be reliable, economical, and environmentally safe.

Endophytic fungi: novel sources of anticancer lead molecules

Endophytic fungi reside in a symbiotic fashion inside their host plants, mimic their chemistry and interestingly, produce the same natural products as their hosts and are thus being screened for the production of valuable compounds like taxol, camptothecin, podophyllotoxin, etc. Vinblastine and vincristine are excellent anti-cancer drugs but their current production using plants is non-abundant and expensive. In order to make these drugs readily available to the patients at affordable prices, we isolated the endophytic fungi from Catharanthus roseus plant and found a fungus AA-CRL-6 which produces vinblastine and vincristine in appreciable amounts. These drugs were purified by TLC and HPLC and characterized using UV-Vis spectroscopy, ESI-MS, MS/MS and 1H NMR. One liter of culture filtrate yielded 76 µg and 67 µg of vinblastine and vincristine respectively. This endophytic fungal strain was identified as Fusarium oxysporum based upon its cultural and morphological characteristics and internal transcribed spacer (ITS) sequence analysis.

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Isolation, purification and characterization of vinblastine and vincristine from endophytic fungus Fusarium oxysporum isolated from Catharanthus roseus.

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

An endophytic fungus, Tax-3, was isolated from barks of Taxus chinensis grown in the Qinba mountains, China. The strain was classified into Fusarium solani based on the morphological characteristics and the molecular phylogenetics inferred from the nuclear ribosomal DNA ITS sequences with the sequence similarity values of 100%. High performance liquid chromatography (HPLC) assay showed the F. solani, Tax-3, produced taxol with a higher yield of 163.35 μg/L in the reformative potato dextrose liquid medium (d), revealing its potential applications for taxol production.

Xiao Wei Ding

Papers

Fusarium solani, Tax-3, a new endophytic taxol-producing fungus from Taxus chinensis.