Abstract
Presently, several drug discovery investigations on therapeutic management of human health are aimed at bioprospecting for microorganisms, especially endophytic microbes of biotechnological importance. This review investigates the benefits of endophytes, especially in producing bioactive compounds useful in modern medicine by systematically reviewing published data from 12 databases. Only experimental studies investigating either or both bacterial and fungal endophytes and within the scope of this review were selected. The published data from the last 2 decades (2000–2019) revealed diverse endophytes associated with different plants produce a broad spectrum of bioactive compounds with therapeutic benefits. Notably, antibacterial, followed by anticancer and antifungal activities, were mostly reported. Only three studies investigated the anti-plasmodial activity. The variation observed in the synthesis of bioactive compounds amongst endophytes varied with host type, endophyte species, and cultivation medium. Fungal endophytes were more investigated than bacterial endophytes, with both endophytes having species diversity amongst literature. The endophytes were predominantly from medicinal plants and belonged to either Ascomycota (fungi) or Proteobacteria and Firmicutes (bacteria). This review presents excellent prospects of harnessing endophytes and their unique bioactive compounds in developing novel and effective compounds of medicinal importance.
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References
Aboobaker Z, Viljoen A, Chen W et al (2019) Endophytic fungi isolated from Pelargonium sidoides DC: antimicrobial interaction and isolation of a bioactive compound. S Afr J Bot 122:535–542. https://doi.org/10.1016/j.sajb.2019.01.011
Abutaha N, Mashaly AMA, Al-Mekhlafi FA et al (2015) Larvicidal activity of endophytic fungal extract of Cochliobolus spicifer (Pleosporales : Pleosporaceae) on Aedes caspius and Culex pipiens (Diptera : Culicidae). Appl Entomol Zool 50:405–414. https://doi.org/10.1007/s13355-015-0347-6
Adeleke RA, Nunthkumar B, Roopnarain A, Obi L (2019a) Applications of plant-microbe interactions in agro-ecosystem. In: Kumar V, Prasad R, Kumar M, Choudhary DK (eds) Microbiome in plant health and disease. Springer Nature, Singapore, pp 1–34
Adeleke RA, Raimi AR, Roopnarain A, Mokubedi SM (2019b) Status and prospects of bacterial inoculants for sustainable management of agroecosystems. In: Giri B, Prasad R, Wu Q-S, Varma A (eds) Biofertilizers for sustainable agriculture and environment, soil biolo. Springer, Cham, pp 137–172
Ali L, Khan AL, Hussain J et al (2016) Sorokiniol: a new enzymes inhibitory metabolite from fungal endophyte Bipolaris sorokiniana LK12. BMC Microbiol 16:1–9. https://doi.org/10.1186/s12866-016-0722-7
Aly AH, Edrada-Ebel R, Wray V et al (2008) Bioactive metabolites from the endophytic fungus Ampelomyces sp. isolated from the medicinal plant Urospermum picroides. Phytochemistry 69:1716–1725. https://doi.org/10.1016/j.phytochem.2008.02.013
Amatuzzi RF, Cardoso N, Poltronieri AS et al (2018) Potential of endophytic fungi as biocontrol agents of Duponchelia fovealis (Zeller) (Lepidoptera : Crambidae). Braz J Microbiol 78:429–435
Anandan K, Vittal RR (2018) Endophytic Paenibacillus amylolyticus KMCLE06 extracted dipicolinic acid as antibacterial agent derived via dipicolinic acid synthetase. Curr Microbiol. https://doi.org/10.1007/s00284-018-1605-y
Andrioli WJ, Silva TM, Vinícius B et al (2012) The fungal metabolite eugenitin as additive for Aspergillus niveus glucoamylase activation. J Mol Catal B Enzym 74:156–161. https://doi.org/10.1016/j.molcatb.2011.08.003
Ariantari NP, Daletos G, Mandi A et al (2019) Expanding the chemical diversity of an endophytic fungus Bulgaria inquinans, an ascomycete associated with mistletoe, through an OSMAC approach. RSC Adv 9:25119–25132. https://doi.org/10.1039/c9ra03678d
Arnold AE (2008) Hidden within our botanical richness, a treasure trove of fungal endophytes. Plant Press 32:13–15
Arora D, Sharma N, Singamaneni V et al (2016a) Isolation and characterization of bioactive metabolites from Xylaria psidii, an endophytic fungus of the medicinal plant Aegle marmelos and their role in mitochondrial dependent apoptosis against pancreatic cancer cells. Phytomedicine 23:1312–1320. https://doi.org/10.1016/j.phymed.2016.07.004
Arora P, Wani ZA, Nalli Y et al (2016b) Antimicrobial potential of thiodiketopiperazine derivatives produced by Phoma sp., an endophyte of Glycyrrhiza glabra Linn. Microb Ecol 72:802. https://doi.org/10.1007/s00248-016-0805-x
Atanda AC, Adeleke RA, Jooste PJ, Madoroba E (2018) Insights into the microbiological safety of vermicompost and vermicompost tea produced by South African smallholder farmers. Indian J Microbiol 58:479–488. https://doi.org/10.1007/s12088-018-0748-7
Ateba JET, Toghueo RMK, Awantu AF et al (2018) Antiplasmodial properties and cytotoxicity of endophytic fungi from Symphonia globulifera (Clusiaceae). J Fungi 4:1–9. https://doi.org/10.3390/jof4020070
Aykul S, Martinez-Hackert E (2016) Determination of half-maximal inhibitory concentration using biosensor-based protein interaction analysis. Anal Biochem 508:97–103. https://doi.org/10.1016/j.ab.2016.06.025
Bacon CW, White JF (2000) Microbial endophytes. Marcel Dekker Inc., New York
Bang S, Song JH, Lee D et al (2019) Neuroprotective secondary metabolite produced by an endophytic fungus, Neosartorya fischeri JS0553, isolated from Glehnia littoralis. J Agric Food Chem 67:1831–1838. https://doi.org/10.1021/acs.jafc.8b05481
Barros FAP, Rodrigues-Filho E (2005) Four spiroquinazoline alkaloids from Eupenicillium sp. isolated as an endophytic fungus from leaves of Murraya paniculata (Rutaceae). Biochem Syst Ecol 33:257–268. https://doi.org/10.1016/j.bse.2004.09.002
Bhalkar BN, Bedekar PA, Patil SM et al (2015) Production of camptothecin using whey by an endophytic fungus: standardization using response. RSC Adv 5:62828–62835. https://doi.org/10.1039/c5ra12212k
Bhatia A, Bharti SK, Tripathi T et al (2015) Metabolic profiling of Commiphora wightii (guggul) reveals a potential source for pharmaceuticals and nutraceuticals. Phytochemistry 10:29–36. https://doi.org/10.1016/j.phytochem.2014.12.016
Blackwell M (2011) The fungi: 1, 2, 3 … 5.1 million species? Am J Bot 98:426–438. https://doi.org/10.3732/ajb.1000298
CancerQuest (2017) Drug development and discovery. In: CancerQuest. https://www.cancerquest.org/patients/discovery-and-development-drugs. Accessed 20 Sep 2020
Casella TM, Eparvier V, Mandavid H et al (2013a) Antimicrobial and cytotoxic secondary metabolites from tropical leaf endophytes: isolation of antibacterial agent pyrrocidine C from Lewia infectoria SNB-GTC2402. Phytochemistry 96:370–377. https://doi.org/10.1016/j.phytochem.2013.10.004
Casella TM, Eparvier V, Mandavid H et al (2013b) Antimicrobial and cytotoxic secondary metabolites from tropical leaf endophytes: isolation of antibacterial agent pyrrocidine C from Lewia infectoria SNB-GTC2402. Phytochemistry 96:370–377
Chatterjee S, Ghosh R, Mandal CN (2019) Production of bioactive compounds with bactericidal and antioxidant potential by endophytic fungus Alternaria alternata AE1 isolated from Azadirachta indica A. Juss. PLoS ONE 14:1–18. https://doi.org/10.1371/journal.pone.0214744
Chen Y-T, Yuan Q, Shan L-T et al (2013) Antitumor activity of bacterial exopolysaccharides from the endophyte Bacillus amyloliquefaciens sp. isolated from Ophiopogon japonicus. Oncol Lett 5:1787–1792
Cui J, Guo T, Ren Z et al (2015) Diversity and antioxidant activity of culturable endophytic fungi from alpine plants of Rhodiola crenulata, R. angusta, and R. sachalinensis. PLoS ONE 10:1–16. https://doi.org/10.1371/journal.pone.0118204
Dahlmann HA (2013) Efficacy of cancer drugs: looking beyond the IC50. Chem Res Toxicol 50:1776–1777. https://doi.org/10.1021/tx400426k
Das M, Prakash HS, Nalini MS (2017) Antioxidative and antibacterial potentials of fungal endophytes from Justicia wynaadensis Heyne: an ethnomedicinal rain forest species of Western Ghats. Asian J Pharm Clin Res 10:203–209. https://doi.org/10.22159/ajpcr.2017.v10i6.18106
de Medeiros AG, Savi DC, Mitra P et al (2018) Bioprospecting of Diaporthe terebinthifolii LGMF907 for antimicrobial compounds. Folia Microbiol 63:499. https://doi.org/10.1007/s12223-018-0587-2
Demain A (2014) Importance of microbial natural products and the need to revitalize their discovery. J Ind Microbiol Biotechnol 41:185–201
Dhayanithy G, Subban K, Chelliah J (2019) Diversity and biological activities of endophytic fungi associated with Catharanthus roseus. BMC Microbiol 19:1–14. https://doi.org/10.1186/s12866-019-1386-x
Egan JM, Kaur A, Raja HA et al (2016) Antimicrobial fungal endophytes from the botanical medicine goldenseal (Hydrastis canadensis). Phytochem Lett 17:219–225. https://doi.org/10.1016/j.phytol.2016.07.031
Ek-Ramos MJ, Gomez-Flores R, Orozco-Flores AA et al (2019) Bioactive products from plant-endophytic gram-positive bacteria. Front Microbiol 10:1–12. https://doi.org/10.3389/fmicb.2019.00463
Faeth SH, Fagan WF (2002) Fungal endophytes: common host plant symbionts but uncommon mutualists. Integr Comp Biol 42:360–368. https://doi.org/10.1093/icb/42.2.360
Fallahi-Sichani M, Honarnejad S, Heiser LM et al (2008) Metrics other than potency reveal systematic variation in responses to cancer drugs. Nat Chem Biol 23:1–7. https://doi.org/10.1038/nchembio.1337.Metrics
Ferus P, Barta M, Konôpková J (2019) Endophytic fungus Beauveria bassiana can enhance drought tolerance in red oak seedlings. Trees 33:1179–1186. https://doi.org/10.1007/s00468-019-01854-1
Firáková S, Šturdíková M, Múčková M (2007) Bioactive secondary metabolites produced by microorganisms associated with plants. Biologia (Bratisl) 62:251–257. https://doi.org/10.2478/s11756-007-0044-1
Gangadevi V, Muthumary J (2008) Taxol, an anticancer drug produced by an endophytic fungus Bartalinia robillardoides Tassi, isolated from a medicinal plant, Aegle marmelos Correa ex Roxb. World J Microbiol Biotechnol 24:717–724. https://doi.org/10.1007/s11274-007-9530-4
George TK, Joy A, Divya K, Jisha MS (2019) In vitro and in silico docking studies of antibacterial compounds derived from endophytic Penicillium setosum. Microb Pathog 131:87–97. https://doi.org/10.1016/j.micpath.2019.03.033
Golinska P, Wypij M, Agarkar G et al (2015) Endophytic actinobacteria of medicinal plants : diversity and bioactivity. Antonie Van Leeuwenhoek 108:267–289. https://doi.org/10.1007/s10482-015-0502-7
Gond SK, Mishra A, Sharma VK et al (2011) Diversity and antimicrobial activity of endophytic fungi isolated from Nyctanthes arbor-tristis, a well-known medicinal plant of India. Mycoscience 53:113–121. https://doi.org/10.1007/s10267-011-0146-z
González-Menéndez V, Crespo G, de Pedro N et al (2018) Fungal endophytes from arid areas of Andalusia: high potential sources for antifungal and antitumoral agents. Sci Rep. https://doi.org/10.1038/s41598-018-28192-5
Gos FMWR, Savi DC, Shaaban KA et al (2017) Antibacterial activity of endophytic actinomycetes isolated from the medicinal plant Vochysia divergens (Pantanal, Brazil). Front Microbiol 8:1–17. https://doi.org/10.3389/fmicb.2017.01642
Gouda S, Das G, Sen SK et al (2016) Endophytes: a treasure house of bioactive compounds of medicinal importance. Front Microbiol 7:1–8. https://doi.org/10.3389/fmicb.2016.01538
Gupta S, Chaturvedi P, Kulkarni MG, Van Staden J (2020) A critical review on exploiting the pharmaceutical potential of plant endophytic fungi. Biotechnol Adv 39:107462. https://doi.org/10.1016/j.biotechadv.2019.107462
Hardoim PR, van Overbeek LS, Berg G et al (2015) The hidden world within plants: ecological and evolutionary considerations for defining functioning of microbial endophytes. Microbiol Mol Biol Rev 79:293–320. https://doi.org/10.1128/mmbr.00050-14
Harrison JG, Griffin EA (2020) The diversity and distribution of endophytes across biomes, plant phylogeny and host tissues: how far have we come and where do we go from here? Environ Microbiol 00:1–17. https://doi.org/10.1111/1462-2920.14968
Harun A, James RMJ, Lim SM et al (2011) BACE1 inhibitory activity of fungal endophytic extracts from Malaysian medicinal plants. BMC Complement Altern Med 11:1–6. https://doi.org/10.1186/1472-6882-11-79
Hazalin NAMN, Ramasamy K, Lim SM et al (2009) Cytotoxic and antibacterial activities of endophytic fungi isolated from plants at the National Park, Pahang Malaysia. BMC Complement Altern Med 9:46. https://doi.org/10.1186/1472-6882-9-46
Higginbotham SJ, Arnold AE, Ibañez A et al (2013) Bioactivity of fungal endophytes as a function of endophyte taxonomy and the taxonomy and distribution of their host plants. PLoS ONE 8:1–11
IDEXX (2019) Microbiology guide to interpreting minimum inhibitory concentration. In: Diagonistic Updat. https://www.idexx.com/files/microbiology-guide-interpreting-mic.pdf. Accessed 23 Oct 2020
Indira K, Jayaprabha N, Srinivasan M (2015) Antimicrobial activity of endophytic fungi isolated and identified from salt marsh plant in Vellar Estuary. J Microbiol Antimicrob 7:13–20. https://doi.org/10.5897/jma2014.0334
Jahn L, Schafhauser T, Wibberg D et al (2017) Linking secondary metabolites to biosynthesis genes in the fungal endophyte Cyanodermella asteris: the anti-cancer bisanthraquinone skyrin. J Biotechnol 257:233–239. https://doi.org/10.1016/j.jbiotec.2017.06.410
Jamwal VL, Gandhi SG (2019) Endophytes as source of high-value phytochemicals: present scenario and future outlook. In: Jha S (ed) Endophytes and secondary metabolites. Springer Nature, Switzerland, pp 1–20
Jasim B, Sreelakshmi KS, Mathew J, Radhakrishnan EK (2016) Surfactin, Iturin, and Fengycin biosynthesis by endophytic Bacillus sp. from Bacopa monnieri. Microb Ecol 72:106–119. https://doi.org/10.1007/s00248-016-0753-5
Jia M, Chen L, Xin HL et al (2016) A friendly relationship between endophytic fungi and medicinal plants: a systematic review. Front Microbiol 7:1–14. https://doi.org/10.3389/fmicb.2016.00906
Jouda J-B, Tamokou J-D, Mbazoa CD et al (2016) Antibacterial and cytotoxic cytochalasins from the endophytic fungus sp. Phomopsis harbored in Garcinia kola (Heckel) nut. BMC Complement Altern Med 16:1–9. https://doi.org/10.1186/s12906-016-1454-9
Kaaniche F, Hamed A, Abdel-Razek AS et al (2019) Bioactive secondary metabolites from new endophytic fungus Curvularia. sp isolated from Rauwolfia macrophylla. PLoS ONE 14:1–12
Kandeil MA, Hashem RM, Mahmoud MO et al (2019) Zingiber officinale extract and omega-3 fatty acids ameliorate endoplasmic reticulum stress in a nonalcoholic fatty liver rat model. J Food Biochem 43:e13076. https://doi.org/10.1111/jfbc.13076
Karimi A, Majlesi M, Rafieian-Kopaei M (2015) Herbal versus synthetic drugs; beliefs and facts. J Nephropharmacol 4:27–30
Katoch M, Singh G, Sharma S et al (2014) Cytotoxic and antimicrobial activities of endophytic fungi isolated from Bacopa monnieri (L.) Pennell (Scrophulariaceae). BMC Complement Altern Med 14:52. https://doi.org/10.1186/1472-6882-14-52
Katoch M, Paul A, Singh G, Sridhar SNC (2017a) Fungal endophytes associated with Viola odorata Linn. as bioresource for pancreatic lipase inhibitors. BMC Complement Altern Med 17:1–8. https://doi.org/10.1186/s12906-017-1893-y
Katoch M, Phull S, Vaid S, Singh S (2017b) Diversity, phylogeny, anticancer and antimicrobial potential of fungal endophytes associated with Monarda citriodora L. BMC Microbiol 17:1–13. https://doi.org/10.1186/s12866-017-0961-2
Katoch M, Singh A, Singh G et al (2017c) Phylogeny, antimicrobial, antioxidant and enzyme-producing potential of fungal endophytes found in Viola odorata. Ann Microbiol 67:529–540. https://doi.org/10.1007/s13213-017-1283-1
Katoch M, Singh D, Kapoor KK, Vishwakarma RA (2019) Trichoderma lixii (IIIM-B4), an endophyte of Bacopa monnieri L. producing peptaibols. BMC Microbiol 19:1–10. https://doi.org/10.1186/s12866-019-1477-8
Kaur G, Dufour JM (2012) Cell lines: valuable tools or useless artifacts. Spermatogenesis 2:1–5. https://doi.org/10.4161/spmg.19885
Khan Z, Rho H, Firrincieli A et al (2016) Growth enhancement and drought tolerance of hybrid poplar upon inoculation with endophyte consortia. Curr Plant Biol 6:38–47. https://doi.org/10.1016/j.cpb.2016.08.001
Khan N, Afroz F, Mst BN et al (2018) Endophytic Fusarium solani: a rich source of cytotoxic and antimicrobial napthaquinone and aza-anthraquinone derivatives. Toxicol Rep 5:970–976. https://doi.org/10.1016/j.toxrep.2018.08.016
Kharwar RN, Mishra A, Gond SK, Stierle D (2011) Anticancer compounds derived from fungal endophytes : their importance and future challenges. Nat Prod Rep 28:1208–1228. https://doi.org/10.1039/c1np00008j
Kharwar RN, Maurya AL, Verma VC et al (2012) Diversity and antimicrobial activity of endophytic fungal community isolated from medicinal plant Cinnamomum camphora. Proc Natl Acad Sci India Sect B Biol Sci 82:557–565. https://doi.org/10.1007/s40011-012-0063-8
Kong W, Huang C, Shi J et al (2019) Recycling of Chinese herb residues by endophytic and probiotic fungus Aspergillus cristatus CB10002 for the production of medicinal valuable anthraquinones. Microb Cell Fact. https://doi.org/10.1186/s12934-019-1150-9
Kouipou Toghueo RM, Boyom FF (2019) Endophytes from ethno-pharmacological plants: sources of novel antioxidants–a systematic review. Biocatal Agric Biotechnol 22:101430. https://doi.org/10.1016/j.bcab.2019.101430
Koul M, Kumar A, Deshidi R et al (2017) Cladosporol A triggers apoptosis sensitivity by ROS-mediated autophagic flux in human breast cancer cells. BMC Cell Biol 18:1–15. https://doi.org/10.1186/s12860-017-0141-0
Kumaran RS, Muthumary J, Kim EK, Hur BK (2009) Production of taxol from Phyllosticta dioscoreae, a leaf spot fungus isolated from Hibiscus rosa-sinensis. Biotechnol Bioprocess Eng 14:76–83. https://doi.org/10.1007/s12257-008-0041-4
Kuriakose GC, Palem PPC, Jayabaskaran C (2016) Fungal vincristine from Eutypella spp - CrP14 isolated from Catharanthus roseus induces apoptosis in human squamous carcinoma cell line -A431. BMC Complement Altern Med 16:1–8. https://doi.org/10.1186/s12906-016-1299-2
Kusari S, Lamshöft M, Spiteller M (2009) Aspergillus fumigatus Fresenius, an endophytic fungus from Juniperus communis L. Horstmann as a novel source of the anticancer pro-drug deoxypodophyllotoxin. J Appl Microbiol 107:1019–1030. https://doi.org/10.1111/j.1365-2672.2009.04285.x
Kyekyeku OJ, Kusari S, Adosraku KR et al (2017) Antibacterial secondary metabolites from an endophytic fungus, Fusarium solani JK10. Fitoterapia 119:108–114. https://doi.org/10.1016/j.fitote.2017.04.007
Lai D, Brötz-Oesterhelt H, Müller WEG et al (2013) Bioactive polyketides and alkaloids from Penicillium citrinum, a fungal endophyte isolated from Ocimum tenuiflorum. Fitoterapia 91:100–106. https://doi.org/10.1016/j.fitote.2013.08.017
Latha P, Karthikeyan M, Rajeswari E (2019) Endophytic bacteria : prospects and applications for the plant disease management. In: Ansari RA, Mahmood I (eds) Plant health under biotic stress. Springer Nature, Singapore, pp 1–50
Li H, Qing C, Zhang Y, Zhao Z (2005) Screening for endophytic fungi with antitumour and antifungal activities from Chinese medicinal plants. World J Microbiol Biotechnol 21:1515–1519. https://doi.org/10.1007/s11274-005-7381-4
Li G, Xu K, Chen W-Q et al (2019) Heptaketides from the endophytic fungus Pleosporales sp. F46 and their antifungal and cytotoxic activities. RSC Adv 9:12913–13129. https://doi.org/10.1039/c9ra01956a
Liang H, Xing Y, Chen J et al (2012) Antimicrobial activities of endophytic fungi isolated from Ophiopogon japonicus (Liliaceae). BMC Complement Altern Med 12:238. https://doi.org/10.1186/1472-6882-12-238
Liu M, Abdel-Mageed W, Ren B et al (2014) Endophytic Streptomyces sp. Y3111 from traditional Chinese medicine produced antitubercular pluramycins. Appl Microbiol Biotechnol 98:1077–1085
Liu Y, Nan L, Liu J et al (2016) Isolation and identification of resveratrol-producing endophytes from wine grape Cabernet Sauvignon. Springerplus 5:1–7. https://doi.org/10.1186/s40064-016-2571-0
Liu J, Wang X, Pu H et al (2017) Recent advances in endophytic exopolysaccharides: production, structural characterization, physiological role and biological activity. Carbohydr Polym 157:1113–1124
Mageshwaran V, Walia S, Annapurna K (2012) Isolation and partial characterization of antibacterial lipopeptide produced by Paenibacillus polymyxa HKA-15 against phytopathogen Xanthomonas campestris pv. phaseoli M-5. World J Microbiol Biotechnol 28:909–917. https://doi.org/10.1007/s11274-011-0888-y
Manganyi MC, Regnier T, Kumar A et al (2018) Biodiversity and antibacterial screening of endophytic fungi isolated from Pelargonium sidoides. S Afr J Bot 116:192–199
Manganyi MC, Tchatchouang C-DK, Regnier T et al (2019) Bioactive compound produced by endophytic fungi isolated from Pelargonium sidoides against selected bacteria of clinical importance. Mycobiology 47:335–339. https://doi.org/10.1080/12298093.2019.1631121
Martinez-Klimova E, Rodríguez-Peña K, Sánchez S (2017) Endophytes as sources of antibiotics. Biochem Pharmacol 134:1–17. https://doi.org/10.1016/j.bcp.2016.10.010
Mashiane AR, Adeleke RA, Bezuidenhout CC, Chirima GJ (2018) Community composition and functions of endophytic bacteria of Bt maize. S Afr J Sci 114:1–10. https://doi.org/10.17159/sajs.2018/20170018
Matloub AA, Gomaa EZ, Hassan AA et al (2019) Comparative chemical and bioactivity studies of intra- and extracellular metabolites of endophytic bacteria, Bacillus subtilis NCIB 3610. Int J Pept Res Ther. https://doi.org/10.1007/s10989-019-09856-w
Mckinnon AC (2016) Plant tissue preparation for the detection of an endophytic fungus in planta. In: Glare TR, Moran-Diez ME (eds) Microbial-based biopesticides. Springer, New York, pp 167–173
Mendes R, Garbeva P, Raaijmakers JM (2013) The rhizosphere microbiome: significance of plant beneficial, plant pathogenic, and human pathogenic microorganisms. FEMS Microbiol Rev 37:634–663
Michael A, Kelman T, Pitesky M (2020) Overview of quantitative methodologies to understand antimicrobial resistance via minimum inhibitory concentration. Animals 10:1–17. https://doi.org/10.3390/ani10081405
Mishra Y, Singh A, Batra A, Sharma MM (2014) Understanding the biodiversity and biological applications of endophytic fungi: a review. J Microb Biochem Technol. https://doi.org/10.4172/1948-5948.s8-004
Mishra VK, Passari AK, Chandra P et al (2017) Determination and production of antimicrobial compounds by Aspergillus clavatonanicus strain MJ31, an endophytic fungus from Mirabilis jalapa L. using UPLC-ESI-MS / MS and TD-GC-MS analysis. PLoS ONE 12:1–24. https://doi.org/10.1371/journal.pone.0186234
Mondal S, Rai VR (2019) Molecular profiling of endophytic Streptomyces cavourensis MH16 inhabiting Millingtonia hortensis Linn. and influence of different culture media on biosynthesis of antimicrobial metabolites. Sci Nat 106:1–10. https://doi.org/10.1007/s00114-019-1646-5
Murugappan RM, Begum SB, Roobia RR (2013) Symbiotic influence of endophytic Bacillus pumilus on growth promotion and probiotic potential of the medicinal plant Ocimum sanctum. Symbiosis 60:91–99. https://doi.org/10.1007/s13199-013-0244-0
Narmani A, Bertrand R, Helaly SE et al (2019) Cytotoxic, anti-biofilm and antimicrobial polyketides from the plant associated fungus Chaetosphaeronema achilleae. Fitoterapia 139:1–6. https://doi.org/10.1016/j.fitote.2019.104390
Nath A, Chattopadhyay A, Joshi SR (2015) Biological activity of endophytic fungi of Rauwolfia serpentina Benth: an ethnomedicinal plant used in folk medicines in Northeast India. Proc Natl Acad Sci India Sect B Biol Sci 85:233–240. https://doi.org/10.1007/s40011-013-0184-8
Newman D (2017) Screening and identification of novel biologically active natural compounds [version 1; referees: 2 approved]. F1000Research 6:1–13. https://doi.org/10.12688/f1000research.11221.1
Noriler SA, Savi DC, Ponomareva LV et al (2019) Vochysiamides A and B: two new bioactive carboxamides produced by the new species Diaporthe vochysiae. Fitoterapia 138:1–7. https://doi.org/10.1016/j.fitote.2019.104273
Ola ARB, Thomy D, Lai D et al (2013) Inducing secondary metabolite production by the endophytic fungus Fusarium tricinctum through coculture with Bacillus subtilis. J Nat Prod 76:2094–2099. https://doi.org/10.1021/np400589h
Padhi S, Tayung K (2013) Antimicrobial activity and molecular characterization of an endophytic fungus, Quambalaria sp. isolated from Ipomoea carnea. Ann Microbiol 63:793–800. https://doi.org/10.1007/s13213-012-0534-4
Palanichamy P, Krishnamoorthy G, Kannan S, Marudhamuthu M (2018) Bioactive potential of secondary metabolites derived from medicinal plant endophytes. Egypt J Basic Appl Sci 5:303–312. https://doi.org/10.1016/j.ejbas.2018.07.002
Palanichamy P, Kannan S, Murugan D et al (2019) Purification, crystallization and anticancer activity evaluation of the compound alternariol methyl ether from endophytic fungi Alternaria alternata. J Appl Microbiol 127:1468–1478. https://doi.org/10.1111/jam.14410
Pandey PK, Kass PH, Soupir ML et al (2014) Contamination of water resources by pathogenic bacteria. AMB Express 4:1–16. https://doi.org/10.1186/s13568-014-0051-x
Parthasarathy A, Gan HM, Wong NH et al (2018) Isolation and genomic characterization of six endophytic bacteria isolated from Saccharum sp (sugarcane): Insights into antibiotic, secondary metabolite and quorum sensing metabolism. J Genomics 6:117–121. https://doi.org/10.7150/jgen.28335
Pathania AS, Guru SK, Ashraf NU et al (2015) A novel stereo bioactive metabolite isolated from an endophytic fungus induces caspase dependent apoptosis and STAT-3 inhibition in human leukemia cells. Eur J Pharmacol 765:75–78. https://doi.org/10.1016/j.ejphar.2015.08.018
Peng QIU, Zhi-xiang F, Jie-wei T et al (2015) Diversity, bioactivities, and metabolic potentials of endophytic actinomycetes isolated from traditional medicinal plants in Sichuan, China. Chin J Nat Med 13:942–953. https://doi.org/10.1016/S1875-5364(15)30102-3
Perveen I, Raza AM, Iqbal T et al (2017) Microbial pathogenesis isolation of anticancer and antimicrobial metabolites from Epicoccum nigrum; endophyte of Ferula sumbul. Microb Pathog J 110:214–224. https://doi.org/10.1016/j.micpath.2017.06.033
Presta L, Bosi E, Fondi M et al (2017) Phenotypic and genomic characterization of the antimicrobial producer Rheinheimera sp. EpRS3 isolated from the medicinal plant Echinacea purpurea: insights into its biotechnological relevance. Res Microbiol 168:293–305. https://doi.org/10.1016/j.resmic.2016.11.001
Pretsch A, Nagl M, Schwendinger K et al (2014) Antimicrobial and anti-inflammatory activities of endophytic fungi Talaromyces wortmannii extracts against acne-inducing bacteria. PLoS ONE 9:e97929–e97929. https://doi.org/10.1371/journal.pone.0097929
Qadri M, Deshidi R, Shah AB et al (2015) An endophyte of Picrorhiza kurroa Royle ex. Benth, producing menthol, phenylethyl alcohol and 3-hydroxypropionic acid, and other volatile organic compounds. World J Microbiol Biotechnol 31:1647–1654. https://doi.org/10.1007/s11274-015-1910-6
Rahman L, Shinwari ZK, Iqrar I et al (2017) An assessment on the role of endophytic microbes in the therapeutic potential of Fagonia indica. Ann Clin Microbiol Antimicrob 16:53. https://doi.org/10.1186/s12941-017-0228-7
Rajamanikyam M, Vadlapudi V, Amanchy R, Upadhyayula SM (2017) Endophytic fungi as novel resources of natural therapeutics. Brazil Arch Biol Technol. https://doi.org/10.1590/1678-4324-2017160542
Rajivgandhi G, Vijayan R, Kannan M (2016) Bioactive materials molecular characterization and antibacterial effect of endophytic actinomycetes Nocardiopsis sp. GRG1 (KT235640) from brown algae against MDR strains of uropathogens. Bioact Mater 1:140–150. https://doi.org/10.1016/j.bioactmat.2016.11.002
Ran X, Zhang G, Li S, Wang J (2017) Characterization and antitumor activity of camptothecin from endophytic fungus Fusarium solani isolated from Camptotheca acuminate. Afr Health Sci 17:566–574. https://doi.org/10.4314/ahs.v17i2.34
Ranjan A, Shankar JT, Singh SK (2016) Antibacterial activity of extract of endophytic fungi of Gymnema sylvestre. Proc Natl Acad Sci India Sect B Biol Sci 86:477–483. https://doi.org/10.1007/s40011-014-0471-z
Ratnaweera PB, de Silva ED, Williams DE, Andersen RJ (2015) Antimicrobial activities of endophytic fungi obtained from the arid zone invasive plant Opuntia dillenii and the isolation of equisetin, from endophytic Fusarium sp. BMC Complement Altern Med 15:1–7. https://doi.org/10.1186/s12906-015-0722-4
Richardson SN, Walker AK, Nsiama TK et al (2014) Griseofulvin-producing Xylaria endophytes of Pinus strobus and Vaccinium angustifolium: evidence for a conifer-understory species endophyte ecology. Fungal Ecol 11:107–113
Richardson SN, Nsiama TK, Walker AK et al (2015) Phytochemistry antimicrobial dihydrobenzofurans and xanthenes from a foliar endophyte of Pinus strobus. Phytochemistry 117:436–443. https://doi.org/10.1016/j.phytochem.2015.07.009
Rodriguez RJ, White JF, Arnold AE, Redman RS (2009) Fungal endophytes: diversity and functional roles: Tansley review. New Phytol 182:314–330. https://doi.org/10.1111/j.1469-8137.2009.02773.x
Russo G, Curcio F, Bulli G et al (2018) Oxidative stress, aging, and diseases. Clin Interv Aging 13:757–772. https://doi.org/10.2147/CIA.S158513
Santiago C, Sun L, Munro MHG, Santhanam J (2014) Polyketide and benzopyran compounds of an endophytic fungus isolated from Cinnamomum mollissimum: biological activity and structure. Asian Pac J Trop Biomed 4:627–632. https://doi.org/10.12980/APJTB.4.2014APJTB-2014-0030
Savi D, Shaaban K, Vargas N et al (2015) Microbispora sp. LGMB259 endophytic actinomycete isolated from Vochysia divergens (Pantanal, Brazil) producing β-carbolines and indoles with biological activity. Curr Microbiol 70:345–354
Seepe HA, Amoo SO, Nxumalo W, Adeleke RA (2019) Antifungal activity of medicinal plant extracts for potential management of Fusarium pathogens. Res Crop 20:399–406
Seo WT, Lim WJ, Kim EJ et al (2010) Endophytic bacterial diversity in the young radish and their antimicrobial activity against pathogens. J Korean Soc Appl Biol Chem 53:493–503. https://doi.org/10.3839/jksabc.2010.075
Septiana E, Sukarno N, Sukarno SP (2017) Endophytic fungi associated with turmeric (Curcuma longa L.) can inhibit histamine-forming bacteria in fish. HAYATI J Biosci 24:46–52
Shahzad R, Khan AL, Ali L et al (2018) Characterization of new bioactive enzyme inhibitors from endophytic Bacillus amyloliquefaciens RWL-1. Molecules 23:1–10. https://doi.org/10.3390/molecules23010114
Sharma D, Pramanik A, Agrawal P (2016) Evaluation of bioactive secondary metabolites from endophytic fungus Pestalotiopsis neglecta BAB-5510 isolated from leaves of Cupressus torulosa D.Don. 3 Biotech 6:1–14
Shen XY, Cheng YL, Cai CJ et al (2014) Diversity and antimicrobial activity of culturable endophytic fungi isolated from moso bamboo seeds. PLoS ONE 9:1–7. https://doi.org/10.1371/journal.pone.0095838
Shu-Chun L, Xin Y, Liang-dong G, Ling L (2011) Cytotoxic isoprenylated epoxycyclohexanediols from the plant endophyte Pestalotiopsis fici. Chin J Nat Med 9:374–379. https://doi.org/10.3724/SP.J.1009.2011.00374
Shweta S, Gurumurthy BR, Ravikanth G et al (2013) Endophytic fungi from Miquelia dentata Bedd., produce the anti-cancer alkaloid, camptothecine. Phytomedicine 20:337–342. https://doi.org/10.1016/j.phymed.2012.11.015
Siew C, Sim F, Lin Y et al (2019) Biocontrol activities of metal-tolerant endophytes against Ganoderma boninense in oil palm seedlings cultivated under metal stress. Biol Control 132:66–71. https://doi.org/10.1016/j.biocontrol.2019.02.001
Sikora RA, Schäfer K, Dababat AA (2007) Modes of action associated with microbially induced in planta suppression of plant-parasitic nematodes. Australas Plant Pathol 36:124–134. https://doi.org/10.1071/AP07008
Silva FdA, Liotti RG, Boleti APdA et al (2018) Diversity of cultivable fungal endophytes in Paullinia cupana (Mart.) Ducke and bioactivity of their secondary metabolites. PLoS ONE 13:e0195874. https://doi.org/10.1371/journal.pone.0195874
Singh B, Sharma P, Kumar A et al (2016) Antioxidant and in vivo genoprotective effects of phenolic compounds identified from an endophytic Cladosporium velox and their relationship with its host plant Tinospora cordifolia. J Ethnopharmacol 194:450–456
Sobreira ACM, Pinto FdCL, Florencio KGD et al (2018) Endophytic fungus Pseudofusicoccum stromaticum produces cyclopeptides and plant related bioactive rotenoids. RSC Adv 8:35575–35586. https://doi.org/10.1039/c8ra06824k
Sridhar KR (2019) Diversity, ecology, and significance of fungal endophytes. In: Jha S (ed) Endophytes and secondary metabolites. Springer Nature, Switzerland, pp 1–40
Stone JK, Bacon CW, White JF (2000) An overview of endophytic microbes: endophytism defined. In: Bacon CW, White JF (eds) Microbial endophytes. Marcel Dekker Inc., New York, pp 3–29
Subban K, Singh S, Subramani R et al (2017) Fungal 7-epi-10-deacetyltaxol produced by an endophytic Pestalotiopsis microspora induces apoptosis in human hepatocellular carcinoma cell line (HepG2). BMC Complement Altern Med 17:1–16. https://doi.org/10.1186/s12906-017-1993-8
Supaphon P, Preedanon S (2019) Evaluation of in vitro alpha-glucosidase inhibitory, antimicrobial, and cytotoxic activities of secondary metabolites from the endophytic fungus, Nigrospora sphaerica, isolated from Helianthus annuus. Ann Microbiol 69:1397–1406. https://doi.org/10.1007/s13213-019-01523-1
Supaphon P, Phongpaichit S, Rukachaisirikul V, Sakayaroj J (2013) Antimicrobial potential of endophytic fungi derived from three seagrass species : Cymodocea serrulata, Halophila ovalis and Thalassia hemprichii. PLoS ONE 8:1–9. https://doi.org/10.1371/journal.pone.0072520
Syed U-HR, Strobel G, Geary B, Sears J (2013) An endophytic Nodulisporium sp. from Central America producing volatile organic compounds with both biological and fuel potential. J Microbiol Biotechnol 23:29–35. https://doi.org/10.4014/jmb.1208.04062
Tapfuma KI, Uche-Okereafor N, Sebola TE et al (2019) Cytotoxic activity of crude extracts from Datura stramonium’s fungal endophytes against A549 lung carcinoma and UMG87 glioblastoma cell lines and LC-QTOF-MS/MS based metabolite profiling. BMC Complement Altern Med. https://doi.org/10.1186/s12906-019-2752-9
Tawfike AF, Romli M, Clements C et al (2019) Isolation of anticancer and anti-trypanosome secondary metabolites from the endophytic fungus Aspergillus flocculus via bioactivity guided isolation and MS based metabolomics. J Chromatogr B 1106–1107:71–83. https://doi.org/10.1016/j.jchromb.2018.12.032
Tidke SA, Kiran S, Giridhar P, Gokare RA (2018) Current understanding and future perspectives of endophytic microbes vis-a-vis production of secondary metabolites. In: Jha S (ed) Endophytes and secondary metabolites. Springer Nature, Cham, pp 1–16
Toghueo RMK, Zabalgogeazcoa I, de Aldana BRV, Boyom FF (2017) Enzymatic activity of endophytic fungi from the medicinal plants Terminalia catappa, Terminalia mantaly and Cananga odorata. South African J Bot 109:146–153. https://doi.org/10.1016/j.sajb.2016.12.021
Toghueo RMK, Sahal D, Zabalgogeazcoa Í et al (2018) Conditioned media and organic elicitors underpin the production of potent antiplasmodial metabolites by endophytic fungi from Cameroonian medicinal plants. Parasitol Res 117:2473–2485. https://doi.org/10.1007/s00436-018-5936-1
Tran-Cong NM, Mandi A, Kurtan T et al (2019) Induction of cryptic metabolites of the endophytic fungus Trichocladium sp. through OSMAC and cocultivation. RSC Adv 9:27279–27288. https://doi.org/10.1039/c9ra05469c
Trenado-Uribe M, Silva-Miranda M, Rivero-Cruz JF et al (2018) Antimycobacterial activity of an anthracycline produced by an endophyte isolated from Amphipterygium adstringens. Mol Biol Rep Int J Mol Cell Biol 45:2563. https://doi.org/10.1007/s11033-018-4424-0
Uche-Okereafor N, Sebola T, Tapfuma K et al (2019) Antibacterial activities of crude secondary metabolite extracts from Pantoea Species obtained from the stem of Solanum mauritianum and their effects on two cancer cell lines. Int J Environ Res Public Health 16:602. https://doi.org/10.3390/ijerph16040602
Venugopalan A, Srivastava S (2015) Endophytes as in vitro production platforms of high value plant secondary metabolites. Biotechnol Adv 33:873–887
Verma VC, Gond SK, Kumar A et al (2009) Endophytic actinomycetes from Azadirachta indica A. Juss.: isolation, diversity, and anti-microbial activity. Microb Ecol 57:749–756. https://doi.org/10.1007/s00248-008-9450-3
Vigneshwari A, Rakk D, Nemeth A et al (2019) Host metabolite producing endophytic fungi isolated from Hypericum perforatum. PLoS ONE 14:1–16. https://doi.org/10.1371/journal.pone.0217060
Wagner MR, Lundberg DS, Del Rio TG et al (2016) Host genotype and age shape the leaf and root microbiomes of a wild perennial plant. Nat Commun 7:1–15. https://doi.org/10.1038/ncomms12151
Wang FW, Jiao RH, Cheng AB et al (2007) Antimicrobial potentials of endophytic fungi residing in Quercus variabilis and brefeldin A obtained from Cladosporium sp. World J Microbiol Biotechnol 23:79–83. https://doi.org/10.1007/s11274-006-9195-4
Wang X, Zhang X, Liu L et al (2015) Genomic and transcriptomic analysis of the endophytic fungus Pestalotiopsis fici reveals its lifestyle and high potential for synthesis of natural products. BMC Genomics 16:1–13. https://doi.org/10.1186/s12864-014-1190-9
Wani ZA, Ashraf N, Mohiuddin T, Riyaz-Ul-Hassan S (2015) Plant-endophyte symbiosis, an ecological perspective. Appl Microbiol Biotechnol 99:2955–2965. https://doi.org/10.1007/s00253-015-6487-3
Wilding JL, Bodmer WF (2014) Cancer cell lines for drug discovery and development. Cancer Res 74:2377–2384. https://doi.org/10.1158/0008-5472.CAN-13-2971
Wu B, Shah SAA, Tao Q-N (2018) Secondary metabolites of endophytic fungus Aspergillus TQ67 from Suaeda glauca. Chin Pharm J 53:504–507
Wulansari D, Jamal Y, Agusta A (2014) Pachybasin, a major metabolite from culture broth of endophytic Coelomyceteous AFKR-18 fungus isolated from a Yellow Moonsheed Plant, Arcangelisia flava (L.) Merr. HAYATI J Biosci 21:95–100. https://doi.org/10.4308/hjb.21.2.95
Xie J, Wu Y-Y, Zhang T-Y et al (2017) New and bioactive natural products from an endophyte of Panax notoginseng. RSC Adv 7:38100–38109. https://doi.org/10.1039/c7ra07060h
Xiong Z-Q, Yang Y-Y, Zhao N, Wang Y (2013) Diversity of endophytic fungi and screening of fungal paclitaxel producer from Anglojap yew, Taxus x media. BMC Microbiol 13:1–10. https://doi.org/10.1186/1471-2180-13-71
Xu F, Wang S, Li Y et al (2018) Yield enhancement strategies of rare pharmaceutical metabolites from endophytes. Biotechnol Lett 40:797–807. https://doi.org/10.1007/s10529-018-2531-6
Yadav M, Yadav A, Kumar S, Yadav JP (2016) Spatial and seasonal influences on culturable endophytic mycobiota associated with different tissues of Eugenia jambolana Lam. and their antibacterial activity against MDR strains. BMC Microbiol 16:1–12
Yan R, Zhang Z, Wang Y et al (2014) Efficient strategy for maintaining and enhancing the huperzine A production of Shiraia sp. Slf14 through inducer elicitation. J Ind Microbiol Biotechnol 41:1175–1179. https://doi.org/10.1007/s10295-014-1461-0
Yu H, Zhang L, Li L et al (2010) Recent developments and future prospects of antimicrobial metabolites produced by endophytes. Microbiol Res 165:437–449
Zilla MK, Qadri M, Pathania AS et al (2013) Bioactive metabolites from an endophytic Cryptosporiopsis sp. inhabiting Clidemia hirta. Phytochemistry 95:291–297. https://doi.org/10.1016/j.phytochem.2013.06.021
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The authors appreciate Dr Obinna Ezeokoli for general contributions and proofreading the manuscript.
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This work was supported by the South African National Research Foundation (NRF) [grant number 116251].
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RA conceptualised the study, AR performed the design, literature search, and analyses, and synthesised the literature. AR also compiled the materials and the data and wrote the manuscript, while both authors reviewed and approved the final manuscript.
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Supplementary Fig. S1: The number of publications reported by countries according to the host plants' collection sites for the review period of 20 years, from 2000 to 2019. The collection site used is based on the information provided in the selected publications. The source articles were multicentric, with most of the studies conducted in India, followed by China, Germany, and Brazil (JPG 281 KB)
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Raimi, A., Adeleke, R. Bioprospecting of endophytic microorganisms for bioactive compounds of therapeutic importance. Arch Microbiol 203, 1917–1942 (2021). https://doi.org/10.1007/s00203-021-02256-z
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DOI: https://doi.org/10.1007/s00203-021-02256-z