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Pharmaceutical Potential of Marine Fungal Endophytes 11 Pharmaceutical Potential of Marine Fungal Endophytes 11 Rajesh Jeewon, Amiirah Bibi Luckhun, Vishwakalyan Bhoyroo, Nabeelah B. Sadeer, Mohamad Fawzi Mahomoodally, Sillma Rampadarath, Daneshwar Puchooa, V. Venkateswara Sarma, Siva Sundara Kumar Durairajan, and Kevin D. Hyde Contents 1 Introduction ................................................................................ 284 2 Biodiversity and Taxonomy of Endophytes ............................................... 285 3 Natural Products from Endophytes ........................................................ 286 4 Marine-Derived Compounds from Endophytes ........................................... 287 5 Antibacterial Agents ....................................................................... 288 6 Marine Fungi as Antiparasitic, Antifungal, and Antiviral Agents ........................ 291 7 Antioxidant Agents ........................................................................ 292 8 Cytotoxic Agents ........................................................................... 293 9 Antidiabetic ................................................................................ 296 10 Miscellaneous Agents ...................................................................... 296 R. Jeewon (*) · A. B. Luckhun · N. B. Sadeer · M. F. Mahomoodally Department of Health Sciences, Faculty of Science, University of Mauritius, Moka, Mauritius e-mail: [email protected]; [email protected]; [email protected]; [email protected] V. Bhoyroo · S. Rampadarath · D. Puchooa Faculty of Agriculture, University of Mauritius, Réduit, Mauritius e-mail: [email protected]; [email protected]; [email protected] V. V. Sarma Department of Biotechnology, School of Life Sciences, Pondicherry University, Pondicherry, India e-mail: [email protected] S. S. K. Durairajan Department of Microbiology, School of Life Sciences, Central University of Tamil Nadu, Thiruvarur, India e-mail: [email protected] K. D. Hyde Center of Excellence in Fungal Research, Mae Fah Luang University, Chiang Rai, Thailand e-mail: [email protected] © Springer Nature Switzerland AG 2019 283 S. Jha (ed.), Endophytes and Secondary Metabolites, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-319-90484-9_6 284 R. Jeewon et al. 11 Source of Novel Molecules ................................................................ 298 12 Conclusion and Future Work .............................................................. 298 References ....................................................................................... 299 Abstract The marine environment is currently well explored as one of the most essential sources regarding to natural products in research, since organisms from oceans have exhibited exceptional biological, biochemical, and biosynthetic potential. Similarly, microorganisms’ natural products represent a substantial area for novel therapeutic compounds search. Many reviews highlighted microbial metabolites as targets for discovery and development of new drugs, especially anticancer, antibiotics, antifungals, and antiparasitics among others. Marine fungal endo- phytes are therefore virtually unlimited sources of novel compounds with numer- ous potential therapeutic applications due to their immense diversity and proven ability to produce natural products of medicinal and pharmaceutical importance, thus inspiring researchers to further study them. This book chapter reviews some of the endophytic fungi isolated from marine sources that produce metabolites with various biological activities against human pathogenic microorganisms. The potential for the exploitation in the pharmaceutical industry and concerns are also discussed. Keywords Fungi · Metabolites · Biological activities · Industry · Medicine · Mangroves 1 Introduction Microorganisms are present everywhere and are very versatile in all ecosystems around the globe. Studies demonstrated that 1% of all bacterial species and less than 5% of fungal species are currently known, and at least 10 million microbial species are unknown, remaining hidden in nature [1]. The marine environment is a huge untapped reservoir for fungal diversity. Jones et al. [2] estimated that there could be up to 10,000 species of marine fungi and currently more than 1100 species are documented [3]. These fungi have a wide distribution and recently a number of new species have been discovered [4–7]. Endophytes, a term introduced in 1866, are microorganisms that reside inter- and intracellularly in plants without causing harm to their host cells [8–11]. Endophytic fungi have been found in every plant species examined, and it is estimated that there are over one million endophytic fungi [12–16]. Interest in endophytes has increased immensely with the discovery of the endophytic fungus Taxomyces andreanae, from Taxus brevifolia, producing the billion dollar anticancer drug paclitaxel (taxol), a diterpinoid used in the treatment of breast and ovarian cancers. However, the industrial-scale production of taxol, although being a promising drug, is not meeting the demand of the world population with respect to the number of cancer patients dying from the disease. According to 11 Pharmaceutical Potential of Marine Fungal Endophytes 285 the World Health Organization [17], between 2008 and 2030, the number of new cancer cases is expected to increase more than 80% in low-income countries, which is twice the rate expected in high-income countries (40%). This alarming fact posits scientists to explore new possibilities to synthesize the compound (taxol) from other sources. Many Taxus species are recognized as good taxol producers, namely, T. baccata, T. chinensis, T. cuspidata, T. media, T. floridana, T. canadensis, T. yunnanensis, T. mairei, T. sumatrana, and T. wallichiana [18]. Interestingly, many non-Taxus species also yield taxol compound such as Cardiospermum halicacabum, Citrus medica, Cupressus sp., Ginkgo biloba, Hibiscus rosa-sinensis, Taxodium distichum, Podocarpus sp., Torreya grandifolia, Terminalia arjuna, and Wollemia nobilis [19]. Indeed, till date it has been found that taxol can be produced by some other endophytic fungi, namely, Metarhizium anisopliae and Cladosporium cladosporioides MD2 producing the compound of interest up to a level of 800 μg/L [20]. Recently, a study conducted by El-Sayed et al. (2018) has demon- strated that fungal endophytes, Aspergillus terreus EFB108, EFB59, and EFB14 isolated from the leaves and twigs of Podocarpus gracilior cork are potent taxol producers [21]. Moreover, El-Maali et al. (2018) proposed a faster and accurate isolation method of taxol from two endophytic fungi, namely, Clasdosporium sphaerospermum and Metarizium anisoplae yielding up to 30.36 and 116.373 μg/L, respectively [22]. More than two decades have elapsed since the notable ground breaking discovery of taxol happened, but importantly numerous bioactive molecules have also been isolated from various endophytic fungi [8, 23]. However, only a handful have been described, which means the opportunity to find new and targeted natural products from endophytic microorganisms in different niches and ecosystems is boundless [24] and fungi can be easily grown under routine culture techniques and hence the potential for discovering a virtually inexhaustible supply of metabolites is high. Additionally, modification of culture conditions alters biosynthetic pathways thus leading to the possibility of producing more novel derivatives [25]. Since endo- phytes are capable of producing compounds similar to their host plants, research on endophytes can help in the preservation of world’s diminishing biodiversity [26]. 2 Biodiversity and Taxonomy of Endophytes Endophytic fungi comprise a highly diverse ecological and taxonomic group. An ecosystem having the greatest biodiversity is the one with the greatest number of endophytes and the most diverse microorganisms [26–28]. Tropical and temperate forests are considered to be the most diverse terrestrial ecosystems, with the greatest number and diversity of endophytic fungi since the plants residing in these regions are in a constant evolutionary race to survive [29–32]. For instance, the isolation of 418 endophyte morphospecies from 83 healthy leaves of Heisteria concinna and Ouratea lucens found in the tropical forest of central Panama demonstrated high diversity in these regions. High diversity is associated with the ability of endophytic 286 R. Jeewon et al. fungi to cope efficiently with environmental conditions due to exchange of infor- mation between them and the higher plant [31, 33]. The oceans, specifically deep- sea hydrothermal vents, mangrove forests, algae, and sponges, have recently been discovered to be an ecological niche with high diversity of endophytes [29, 34, 35]. Endophytes are also widely distributed in marine sources especially in sponges and algae with a higher ratio of new compounds to known compounds from algicolous fungi (3.1:1) as compared to sponge-derived fungi (1.4:1) [30, 36–38]. Endophytic fungi are therefore detected in all plants such as algae, mosses, ferns, and numerous angiosperms and gymnosperms including plants from tropical, temperate, and boreal forests, as well as those from extreme arctic, alpine, and xeric environments [36, 39]. Taxonomically, most of the endophytic fungi belong to the phylum Ascomycota and its associated anamorphs, while some species belong to the phyla Basidiomycota and Zygomycota [31]. The majority of these isolates belonged to ubiquitous genera (e.g.,
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