June 2017  Vol. 27  No. 6 J. Microbiol. Biotechnol. (2017), 27(6), 1039–1052 https://doi.org/10.4014/jmb.1701.01036 Research Article jmb Review Marine Algicolous Endophytic Fungi - A Promising Drug Resource of the Era Manomi Sarasan 1† , Jayesh Puthumana 2† , Neema Job 1 , Jeonghoon Han 2 , Jae-Seong Lee 2 * , and Rosamma Philip 1 * Department of Marine Biology, Microbiology, and Biochemistry, School of Marine Sciences, Cochin University of Science and Technology, Kochi-682016, Kerala, India Department of Biological Science, College of Science, Sungkyunkwan University, Suwon 16419, Republic of Korea Introduction In one of the primal articles regarding endophytism, Petrini [1] stated these were all organisms inhabiting plant organs that at some time in their life can colonize internal plant tissue without causing apparent harm to the host. They cause no overt tissue damage hence producing no symptoms, and in fact, there exists no evidence for even their presence in plants [2]. Collectively, the fungal survey of various hosts have suggested the ubiquity of endophytes and revealed their symbiotic association in all healthy plant taxa studied to date, typically more than one guest in each flora [3, 4]. Being non-organ-specific, endophytes invade all organs and reside entirely within plant tissues beneath the epidermal cells, intracellularly or intercellularly [5-7]. In general, endophytes include fungi, bacteria, mycoplasma, and archaebacteria, and the most frequently observed candidates might be “mycoendophytes” [4]. To date, most reviews have focused on highly diverse, polyphyletic assemblages of endophytic ascomycetous fungi, with Aspergillus sp. as the dominant taxa [3, 8]. Fungal endophytes have profound effects on stimulation of plant growth, increased disease resistance, improvement of the plant’s ability to withstand environmental stresses, and recycling of nutrients [9]. Besides these, endophytes may possibly produce a surfeit of bioactive metabolites as the outcome of an intimate relationship with the host, and may serve as potential sources of novel natural products for exploitation in medicine, agriculture, and industry [10]. Several studies do indicate that the active principle of fungal endophytes expresses more activity than those of their respective hosts [2]. A diverse array of novel, eco- Received: January 13, 2017 Revised: April 2, 2017 Accepted: April 3, 2017 First published online April 5, 2017 *Corresponding authors R.P. Phone: +91-484-236-8120; E-mail: rose@cusat.ac.in J.-S.L. Phone: +82-31-290-7011; E-mail: jslee2@skku.edu These authors contributed equally to this work. upplementary data for this paper are available on-line only at http://jmb.or.kr. pISSN 1017-7825, eISSN 1738-8872 Copyright © 2017 by The Korean Society for Microbiology and Biotechnology Endophytic fungi have currently been acknowledged as the most promising source of bioactive compounds for drug discovery, and considerable progress has been made in exploring their diversity, species richness, and bioprospecting. Fungal endophytes from unique environmental settings offer a pool of potentially useful medicinal entities. Owing to the constant stresses imposed on macroalgae by marine environments, it is believed that algae and their associated endophytic symbionts represent a good source of structurally diverse bioactive secondary metabolites. Despite the proven significance of active metabolites of algal endophytes, little have been exploited. This review highlights the latest discoveries in algicolous endophytic research, with particular focus on the bioactive metabolites from algal endophytes. Compounds are classified according to their reported biological activities, like anticancer, antibacterial, antifungal, and antioxidant properties. Present experimental evidence suggests that a majority of the bioactive metabolites were reported from Phaeophyceae followed by Rhodophyceae and Chlorophyceae. An intensive search for newer and more effective bioactive metabolites has generated a treasure trove of publications, and this review partially covers the literature published up to 2016. Keywords: Macroalgae, endophytic fungi, secondary metabolite, bioactive compound, anticancer, antimicrobial S S