Abstract
Background: Endophytes represent a complex community of microorganisms colonizing asymptomatically internal tissues of higher plants. Several reports have shown that endophytes enhance the fitness of their host plants by direct production of bioactive secondary metabolites, which are involved in protecting the host against herbivores and pathogenic microbes. In addition, it is increasingly apparent that endophytes are able to biosynthesize medicinally important “phytochemicals”, originally believed to be produced only by their host plants.
Objective: The present review provides an overview of secondary metabolites from endophytic fungi with pronounced biological activities covering the literature between 2010 and 2017. Special focus is given on studies aiming at exploration of the mode of action of these metabolites towards the discovery of leads from endophytic fungi. Moreover, this review critically evaluates the potential of endophytic fungi as alternative sources of bioactive “plant metabolites”. Results: Over the past few years, several promising lead structures from endophytic fungi have been described in the literature. In this review, 65 metabolites are outlined with pronounced biological activities, primarily as antimicrobial and cytotoxic agents. Some of these metabolites have shown to be highly selective or to possess novel mechanisms of action, which hold great promises as potential drug candidates. Conclusion: Endophytes represent an inexhaustible reservoir of pharmacologically important compounds. Moreover, endophytic fungi could be exploited for the sustainable production of bioactive “plant metabolites” in the future. Towards this aim, further insights into the dynamic endophyte - host plant interactions and origin of endophytic fungal genes would be of utmost importance.Keywords: Endophytes, host plants, natural products, plant metabolites, biological activity, mode of action, lead structures.
[http://dx.doi.org/10.1039/b100918o] [PMID: 11548053]
[http://dx.doi.org/10.3389/fmicb.2016.00906] [PMID: 27375610]
[http://dx.doi.org/10.1016/j.pbi.2006.05.001] [PMID: 16713330]
[http://dx.doi.org/10.2174/092986712800672111] [PMID: 22489725]
[http://dx.doi.org/10.1039/b609472b] [PMID: 17003908]
[http://dx.doi.org/10.1039/C4NP00166D] [PMID: 26038303]
[http://dx.doi.org/10.1039/c1np00008j] [PMID: 21455524]
[http://dx.doi.org/10.1007/s10529-015-1814-4] [PMID: 25792513]
[http://dx.doi.org/10.1021/jf204105k] [PMID: 22435921]
[http://dx.doi.org/10.2174/1872208311666170215151834] [PMID: 28215141]
[http://dx.doi.org/10.1007/s00253-011-3270-y] [PMID: 21523479]
[http://dx.doi.org/10.1039/c2np00073c] [PMID: 22249927]
[http://dx.doi.org/10.1016/j.micres.2013.12.009] [PMID: 24582778]
[http://dx.doi.org/10.1017/CBO9781139946575.003]
[http://dx.doi.org/10.3390/md16090319] [PMID: 30205507]
[http://dx.doi.org/10.2174/0929867322666150716115300] [PMID: 26179997]
[http://dx.doi.org/10.1007/s13213-012-0442-7]
[http://dx.doi.org/10.1039/C4RA11756E]
[http://dx.doi.org/10.1039/b807365a] [PMID: 18820760]
[http://dx.doi.org/10.1021/jo402066b] [PMID: 24295452]
[http://dx.doi.org/10.1038/s41419-018-0312-8] [PMID: 29459714]
[http://dx.doi.org/10.1021/jm400034b] [PMID: 23484593]
[http://dx.doi.org/10.1038/ja.2015.103] [PMID: 26506860]
[http://dx.doi.org/10.1021/np3006666] [PMID: 23387901]
[http://dx.doi.org/10.1021/np4005745] [PMID: 24328302]
[http://dx.doi.org/10.1016/bs.acr.2018.02.006] [PMID: 29551127]
[http://dx.doi.org/10.1055/s-0034-1368301] [PMID: 24710897]
[http://dx.doi.org/10.1093/nar/9.18.4709] [PMID: 6795595]
[PMID: 8306334]
[http://dx.doi.org/10.1098/rstb.1994.0111] [PMID: 7846128]
[http://dx.doi.org/10.1080/02652030500058403] [PMID: 16019807]
[http://dx.doi.org/10.1128/AEM.48.6.1176-1180.1984] [PMID: 6517584]
[http://dx.doi.org/10.1021/jf501724a] [PMID: 24909753]
[http://dx.doi.org/10.1039/C6RA27306H]
[http://dx.doi.org/10.1021/acs.jnatprod.6b00960] [PMID: 28139929]
[http://dx.doi.org/10.1186/s12860-017-0141-0] [PMID: 28728544]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-3914] [PMID: 17440056]
[http://dx.doi.org/10.1016/j.biopha.2017.08.069] [PMID: 28858734]
[http://dx.doi.org/10.1021/jm301816a] [PMID: 23534483]
[http://dx.doi.org/10.1021/acs.jnatprod.5b00436] [PMID: 26905687]
[http://dx.doi.org/10.1021/acsinfecdis.7b00055] [PMID: 29108416]
[http://dx.doi.org/10.1021/np400762k] [PMID: 24251417]
[http://dx.doi.org/10.1021/jf503846z] [PMID: 25350301]
[http://dx.doi.org/10.1021/jf500390h] [PMID: 24708412]
[http://dx.doi.org/10.1021/np400988a] [PMID: 25237727]
[http://dx.doi.org/10.1021/acs.jnatprod.5b00717] [PMID: 26539727]
[http://dx.doi.org/10.1039/C5RA18121F]
[http://dx.doi.org/10.1021/acs.jnatprod.6b00610] [PMID: 28257197]
[http://dx.doi.org/10.1021/np500111w] [PMID: 25356913]
[http://dx.doi.org/10.1021/acs.jnatprod.5b00170] [PMID: 26186257]
[http://dx.doi.org/10.1021/np300327y] [PMID: 22924467]
[http://dx.doi.org/10.1021/np2009913] [PMID: 22486738]
[http://dx.doi.org/10.1021/jf304314g] [PMID: 23214998]
[http://dx.doi.org/10.1016/j.bmcl.2015.08.063] [PMID: 26343828]
[http://dx.doi.org/10.1021/acs.jnatprod.7b00054] [PMID: 29035525]
[http://dx.doi.org/10.1021/ja00738a045] [PMID: 5553076]
[http://dx.doi.org/10.1126/science.8097061] [PMID: 8097061]
[http://dx.doi.org/10.1007/s10295-013-1320-4] [PMID: 23958913]
[http://dx.doi.org/10.1007/s00284-008-9270-1] [PMID: 19484305]
[http://dx.doi.org/10.1099/13500872-142-2-435] [PMID: 8932715]
[http://dx.doi.org/10.1021/np060174f] [PMID: 16933860]
[http://dx.doi.org/10.1007/s00253-013-5163-8] [PMID: 23949997]
[http://dx.doi.org/10.1021/np070669k] [PMID: 18220354]
[http://dx.doi.org/10.1016/j.phytochem.2009.09.030] [PMID: 19863979]
[http://dx.doi.org/10.1021/np800455b] [PMID: 19119919]
[http://dx.doi.org/10.1039/c1np00030f] [PMID: 21629952]
[http://dx.doi.org/10.1038/s41598-017-07886-2] [PMID: 28831055]
[http://dx.doi.org/10.1007/s13225-013-0228-7]
[http://dx.doi.org/10.3389/fmicb.2016.01774] [PMID: 27895623]
[http://dx.doi.org/10.1007/BF01574772]
[http://dx.doi.org/10.1007/s11274-007-9530-4]
[http://dx.doi.org/10.1186/1471-2164-15-69] [PMID: 24460898]
[http://dx.doi.org/10.1006/fgbi.1998.1095] [PMID: 9917370]
[http://dx.doi.org/10.1016/j.phytochem.2009.05.020] [PMID: 19560174]
[http://dx.doi.org/10.1016/j.tibtech.2014.03.009] [PMID: 24703621]
[http://dx.doi.org/10.3389/fpls.2016.00955] [PMID: 27446181]
[http://dx.doi.org/10.1021/np1008398] [PMID: 21348469]
[PMID: 23923629]
[http://dx.doi.org/10.1021/np400955q] [PMID: 24456525]
[http://dx.doi.org/10.3389/fmicb.2013.00003] [PMID: 23346084]
[http://dx.doi.org/10.1201/9781315117089-9]
[http://dx.doi.org/10.1146/annurev-phyto-080508-081831] [PMID: 19400639]
[http://dx.doi.org/10.1016/j.chembiol.2012.06.004] [PMID: 22840767]