Bioprospecting - Secondary metabolites, Antibiotics, antiviral agents, immunosuppressive agents and therapeutic agents

  Secondary metabolites

    Plants select competent endophytes from the environment for their own ecological benefit. Many diverse and highly specialized secondary metabolites and enzymes are produced by the inhabiting microorganisms. Microbial production of manifold molecules like phytohormones, antibiotics and quorum-sensing molecules has been reported in plants. Cytokinins and auxins are plant growth regulators expressed by a vast amount of microbes, especially bacteria. Microbial indole 3-acetic acid production can be of importance to plants, either beneficial by promoting root development or harmful as in crown gall formation induced by Agrobacterium tumefaciens.

 Antibiotics

    Penicillin, the classical example of  natural antibiotics is produced by Penicillium spp. Streptomycin is produced by Streptomyces spp. The production of such compounds is common among microorganisms. Examples of antimicrobial compounds synthesized by plant associated microbes include cyclosporine that is produced by the endophytic fungus Tolypocladium inflatum and shows antifungal activity.  Bioactive compounds produced by plant associated microbes display antiviral activity also. Xiamycin from Streptomyces sp. is reported to have anti-HIV properties.

Antifungal ecomycins derived from the plant endophyte Pseudomonas viridiflava. The ecomycins are active against such human-pathogenic fungi as Cryptococcus neoformans and C. albicans. Another group of antifungal compounds is the Pseudomycins, produced by a plant-associated pseudomonad. They are active against a variety of plant- and human-pathogenic fungi. Pseudomycins are also effective against a number of ascomycetous fungi, they are also being considered for agricultural use. Ambuic acid, a cyclohexenone produced by a number of isolates of Pestalotiopsis microspora found in rainforests around the world, possesses antifungal activity. 

Antifungal peptide cryptocandin, produced by Cryptosporiopsis quercina is active against a number of plant-pathogenic fungi. Cryptocandin and its related compounds are in use against a number of fungi causing diseases of skin and nails. Cryptocin, possesses potent activity against  plant-pathogenic fungi. Antibiotics Turbomycin A and B are isolated from a soil derived metagenomic library.

Antiviral Compounds

Endophytic microorganisms also produce antiviral agents which cause inhibition of viruses. Two novel human cytomegalovirus protease inhibitors, cytonic acids A and B, have been isolated from the endophytic fungus Cytonaema sp. The potential for the discovery of compounds, from endophytes, having antiviral activity is in its infancy. However, some compounds have been found is promising. The main limitation in compound discovery is related to the absence of appropriate antiviral screening systems in most compound discovery programs.

Immunosuppressive Compounds 

Immunosuppressive drugs are used today to prevent allograft rejection in transplant patients, and in the future they could be used to treat autoimmune diseases such as rheumatoid arthritis and insulin-dependent diabetes. The endophytic fungus Fusarium subglutinans, isolated from Tripterygium wilfordii, produces the immunosuppressive, non-cytotoxic diterpene pyrones subglutinol A and B. The fungus Tolypocladium inflatum from which cyclosporine, a beneficial immunosuppressant, was isolated is another example

Anticancer Agents from Endophytic Fungi

    Paclitaxel, the world's first billion-dollar anticancer drug, is produced by many endophytic fungi,  Taxomyces andreanae.  T. andreanae is found symbiotically associated living within yew tree, Taxus brevifolia. Paclitaxel is used to treat a number of other human tissue-proliferating diseases as well. Trichothecium sp, Pestalotiopsis microspora, Tubercularia and many novel endophytic fungal species produce paclitaxel to protect their respective host plant from degradation and disease caused by plant pathogens. Torreyanic acid, another anticancer agent was isolated from a Pestalotiopsis microspora strain. Fungal genera as Xylaria, Phoma, etc produce cytochalasins, compounds with antitumor and antibiotic activities

Antioxidants from Endophytes

Pestacin and Isopestacin, obtained from culture fluids of P. microspora, has antimicrobial as well as antioxidant activity.

Insecticidal compounds from Endophytes 

Nodulisporic acids, which are indole diterpenes exhibiting potent insecticidal properties are isolated from an endophyte, a Nodulisporium sp., from the plant Bontia daphnoides. Another endophytic fungus, Muscodor vitigenus, yields naphthalene as its major product. Naphthalene, the active ingredient in common mothballs, is a widely exploited insect repellant. 

Antidiabetic Agents from Rainforest Fungi

An endophytic fungus, Pseudomassaria sp. collected from an African rainforest produces an antidiabetic compound which acts like insulin but, unlike insulin, is not destroyed in the digestive tract and may be given orally. These results may lead to new therapies for diabetes