BIOACTIVE SECONDARY METABOLITES DERIVED FROM ENDOPHYTES: A REVIEW
DOI:
https://doi.org/10.22159/ajpcr.2025v18i5.53898Keywords:
Endophytes, secondary metabolites, bioactive compounds, plant-microbe interactions, biopharmaceuticals, sustainable agriculture, biotechnology.Abstract
Endophytes comprise diverse bacteria, fungi, and actinomycetes that reside harmlessly within plant tissues, fostering complex ecological interactions that significantly enhance plant growth, stress resilience, and disease resistance. Since their discovery in the early 19th century, endophytes have become essential for sustainable agriculture, environmental conservation, and advances in therapy. They generate bioactive secondary metabolites such as paclitaxel (Taxol), camptothecin, podophyllotoxin, and vincristine, critically important in cancer treatment. The varied biosynthetic pathways for metabolites like terpenoids, polyketides, alkaloids, flavonoids, and phenylpropanoids emphasize the biochemical versatility of endophytes. Leveraging these bacteria biotechnologically offers a sustainable and scalable alternative to conventional plant-based extraction, addressing the growing global demand for medicinal compounds while minimizing ecological impact. This review presents a detailed analysis of endophytes' classification, ecological roles, and industrial applications, highlighting their significant contributions to advanced pharmaceutical research, sustainable agriculture, and bioremediation. Expanding research on plant-endophyte relationships may result in discovering new bioactive compounds, advancing the convergence of microbiology, biotechnology, and environmental science.
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Bhunjun CS, Phukhamsakda C, Hyde KD, McKenzie EH, Saxena RK, Li Q. Do all fungi have ancestors with endophytic lifestyles? Fungal Divers. 2023;125(1):73-98. doi: 10.1007/s13225-023-00516-5
Singh N, Sharma V, Kalita RD. Interaction between plants and endophytes: Evolutionary significance and its role in plants development. In: Plant Endophytes and Secondary Metabolites. Netherlands: Elsevier; 2024. p. 295-312. doi: 10.1016/B978-0-443- 13365-7.00007-5
Rabbee MF, Ali MS, Islam MN, Rahman MM, Hasan MM, Baek KH. Endophyte mediated biocontrol mechanisms of phytopathogens in agriculture. Res Microbiol. 2024;175(8):104229. doi: 10.1016/j. resmic.2024.104229. PMID 38992820
Muthu Narayanan M, Ahmad N, Shivanand P, Metali F. The role of endophytes in combating fungal- and bacterial-induced stress in plants. Molecules. 2022;27(19):6549. doi: 10.3390/molecules27196549, PMID 36235086
Hardoim PR, van Overbeek LS, Berg G, Pirttilä AM, Compant S, Campisano A, et al. The hidden world within plants: ecological and evolutionary considerations for defining functioning of microbial endophytes. Microbiol Mol Biol Rev. 2015;79(3):293-320. doi: 10.1128/MMBR.00050-14, PMID 26136581
Potshangbam M, Devi SI, Sahoo D, Strobel GA. Functional characterization of endophytic fungal community associated with Oryza sativa L. and Zea mays L. Front Microbiol. 2017;8:325. doi: 10.3389/fmicb.2017.00325, PMID 28303127
Singh R, Dubey AK. Endophytic Actinomycetes as emerging source for therapeutic compounds. Indo Glob J Pharm Sci. 2015;5(2):106-16. doi: 10.35652/IGJPS.2015.11
Bard NW, Cronk QC, Davies TJ. Fungal endophytes can modulate plant invasion. Biol Rev Camb Philos Soc. 2024;99(5):1652-71. doi: 10.1111/brv.13085, PMID 38629189
Liu S, Hou Y, Zheng K, Ma Q, Wen M, Shao S, et al. Exploring the diversity, bioactivity of endophytes, and metabolome in Synsepalum dulcificum. Front Microbiol. 2024;15:1258208. doi: 10.3389/ fmicb.2024.1258208, PMID 38476934
Kharkwal AC, Joshi H, Shandilya C, Dabral S, Kumar N, Varma A. Isolation and characterization of a newly discovered plant growth-promoting endophytic fungal strain from the genus Talaromyces. Sci Rep. 2024;14(1):6022. doi: 10.1038/s41598-024-54687-5, PMID 38472228
Gouda S, Das G, Sen SK, Shin HS, Patra JK. Endophytes: A treasure house of bioactive compounds of medicinal importance. Front Microbiol. 2016;7:1538. doi: 10.3389/fmicb.2016.01538, PMID 27746767
Das S, Das M, Nath R, Nath D, Patra JK, Talukdar AD. Fungal metabolites and their importance in pharmaceutical industry. In: Entrepreneurship with microorganisms. Netherlands: Elsevier; 2024. p. 89-120. doi: 10.1016/B978-0-443-19049-0.00021-9
Prakash V, Rana S, Sagar A. Taxomyces andreanae: A source of anticancer drug. Int J Bot Stud. 2016;1:43-6.
Liang Z, Zhang J, Zhang X, Li J, Zhang X, Zhao C. Endophytic fungus from Sinopodophyllum emodi (Wall.) ying that produces podophyllotoxin. J Chromatogr Sci. 2016;54(2):175-8. doi: 10.1093/ chromsci/bmv124, PMID 26306574
Alam M, Pandit B, Moin A, Iqbal UN. Invisible inhabitants of plants and a sustainable planet: Diversity of bacterial endophytes and their potential in sustainable agriculture. Indian J Microbiol. 2024;5:1-24.
Vincze ÉB, Becze A, Laslo É, Mara G. Beneficial soil microbiomes and their potential role in plant growth and soil fertility. Agriculture. 2024;14(1):1-23. doi: 10.3390/agriculture14010152
Liu H, Carvalhais LC, Crawford M, Singh E, Dennis PG, Pieterse CM, et al. Inner plant values: Diversity, colonization and benefits from endophytic bacteria. Front Microbiol. 2017;8:2552. doi: 10.3389/ fmicb.2017.02552, PMID 29312235
Sena L, Mica E, Valè G, Vaccino P, Pecchioni N. Exploring the potential of endophyte-plant interactions for improving crop sustainable yields in a changing climate. Front Plant Sci. 2024;15:1349401. doi: 10.3389/ fpls.2024.1349401, PMID 38571718
Retnowati Y, Kandowangko NY, Katili AS, Pembengo W. Diversity of actinomycetes on plant rhizosphere of karst ecosystem of Gorontalo, Indonesia. Biodiversitas. 2024;25(3):907-15. doi: 10.13057/biodiv/d250301
Tiwari P, Bose SK, Park KI, Dufossé L, Fouillaud M. Plant-microbe interactions under the extreme habitats and their potential applications. Microorganisms. 2024;12(3):448. doi: 10.3390/ microorganisms12030448, PMID 38543499
Wannawong T, Mhuantong W, Macharoen P, Niemhom N, Sitdhipol J, Chaiyawan N, et al. Comparative genomics reveals insight into the phylogeny and habitat adaptation of novel Amycolatopsis species, an endophytic Actinomycete associated with scab lesions on potato tubers. Front Plant Sci. 2024;15:1346574. doi: 10.3389/fpls.2024.1346574, PMID 38601305
Verma VC, Gange AC. Advances in Endophytic Research. Berlin: Springer; 2014. p. 1-454.
Diwthe PC, Sawarkar DA, Umap DS, Somkuwar DA. Endophytes and their therapeutic application. Int J Adv Biochem Res. 2024;8(1):399- 410. doi: 10.33545/26174693.2024.v8.i1f.434
Abdel-Razek AS, El-Naggar ME, Allam A, Morsy OM, Othman SI. Microbial natural products in drug discovery. Processes. 2020;8(4):470. doi: 10.3390/pr8040470
Dastogeer KM, Tumpa FH, Sultana A, Akter MA, Chakraborty A. Plant microbiome-an account of the factors that shape community composition and diversity. Curr Plant Biol. 2020;23:100161. doi: 10.1016/j.cpb.2020.100161
Clay K, Schardl C. Evolutionary origins and ecological consequences of endophyte symbiosis with grasses. Am Nat. 2002;160 Suppl4:S99-S127. doi: 10.1086/342161, PMID 18707456
Qin S, Xing K, Jiang JH, Xu LH, Li WJ. Biodiversity, bioactive natural products and biotechnological potential of plant-associated endophytic Actinobacteria. Appl Microbiol Biotechnol. 2011;89(3):457-73. doi: 10.1007/s00253-010-2923-6, PMID 20941490
Dutta P, Mahanta M, Singh SB, Thakuria D, Deb L, Kumari A, et al. Molecular interaction between plants and Trichoderma species against soil-borne plant pathogens. Front Plant Sci. 2023;14:1145715. doi: 10.3389/fpls.2023.1145715, PMID 37255560
Matsumura E, Morinaga K, Fukuda K. Host Specificity and seasonal variation in the colonization of Tubakia sensu lato associated with evergreen Oak Species in Eastern Japan. Microb Ecol. 2023;86(1):240- 52. doi: 10.1007/s00248-022-02067-9, PMID 35857039
Asad S, Priyashantha AK, Tibpromma S, Luo Y, Zhang J, Fan Z, et al. Coffee-associated endophytes: Plant growth promotion and crop protection. Biology (Basel). 2023;12(7):911. doi: 10.3390/ biology12070911, PMID 37508343
Glazer AN, Nikaido H. Developments in Applied Microbiology and Biotechnology. Cambridge: Cambridge University Press; 2007. p. 45- 67.
Bala K, Ghosh T, Kumar V, Sangwan P. Harnessing Microbial Potential for Multifarious Applications. Cham: Springer Nature; 2024. p. 299- 315.
Marinković J, Nikolić B, Marković T, Petrović B, Pašalić S, Lal M, et al. Essential oils as adjuvants in endodontic therapy: Myth or reality? Future Microbiol. 2022;17:1487-99. doi: 10.2217/fmb-2022-0115, PMID 36321479
Maheshwari DK, Maheshwari R, Rinaudo. Endophytes: Biology and Biotechnology. New York: Springer; 2017. p. 120-30.
Debnath S, Chakraborty S, Langthasa M, Choure K, Agnihotri V, Srivastava A, et al. Non-rhizobial nodule endophytes improve nodulation, change root exudation pattern and promote the growth of lentil for prospective application in fallow soil. Front Plant Sci. 2023;14:1152875. doi: 10.3389/fpls.2023.1152875, PMID 37113600
Patel HK, Makampara RA, Kalaria RK, Joshi MP. Endophytes: A novel tool for sustainable agriculture. In: Endophytic Association: What, Why and How. Netherlands: Elsevier; 2023. p. 37-55. doi: 10.1016/B978-0- 323-91245-7.00023-7
Rani S, Kumar P, Dahiya P, Maheshwari R, Dang AS, Suneja P. Endophytism: A multidimensional approach to plant-prokaryotic microbe interaction. Front Microbiol. 2022;13:861235. doi: 10.3389/ fmicb.2022.861235, PMID 35633681
Anand U, Pal T, Yadav N, Singh VK, Tripathi V, Choudhary KK, et al. Current scenario and future prospects of endophytic microbes: promising candidates for abiotic and biotic stress management for agricultural and environmental sustainability. Plant-Microbe Interact. 2023;8:1455-86.
Afzal I, Shinwari ZK, Sikandar S, Shahzad S. Plant beneficial endophytic bacteria: Mechanisms, diversity, host range and genetic determinants. Microbiol Res. 2019;221:36-49. doi: 10.1016/j.micres.2019.02.001, PMID 30825940
De Mandal S, Jeon J. Phyllosphere Microbiome in plant health and disease. Plants (Basel). 2023;12(19):3481. doi: 10.3390/ plants12193481, PMID 37836221
Nair DN, Padmavathy S. Impact of endophytic microorganisms on plants, environment and humans. ScientificWorldJournal. 2014;2014:250693. doi: 10.1155/2014/250693, PMID 24587715
Jacob J, Krishnan GV, Thankappan D, Amma BN. Endophytic Bacterial Strains Induced Systemic Resistance in Agriculturally Important Crop Plants. Netherlands: Elsevier Incorporated; 2020. p. 75-105.
Trivedi P, Leach JE, Tringe SG, Sa T, Singh BK. Plant-microbiome interactions: From community assembly to plant health. Nat Rev Microbiol. 2020;18(11):607-21. doi: 10.1038/s41579-020-0412-1, PMID 32788714
Verma SK, Sahu PK, Kumar K, Pal G, Gond SK, Kharwar RN, et al. Endophyte roles in nutrient acquisition, root system architecture development and oxidative stress tolerance. J Appl Microbiol. 2021;131(5):2161-77. doi: 10.1111/jam.15111, PMID 33893707
Zhuang Y, Wang H, Tan F, Wu B, Liu L, Qin H, et al. Rhizosphere metabolic cross-talk from plant-soil-microbe tapping into agricultural sustainability: Current advance and perspectives. Plant Physiol Biochem. 2024;210:108619. doi: 10.1016/j.plaphy.2024.108619, PMID 38604013
Ling N, Wang T, Kuzyakov Y. Rhizosphere bacteriome structure and functions. Nat Commun. 2022;13(1):836. doi: 10.1038/s41467-022- 28448-9, PMID 35149704
Mandal M, Das S, Roy A, Rakwal R, Jones OA, Popek R, et al. Interactive relations between plants, the phyllosphere microbial community, and particulate matter pollution. Sci Total Environ. 2023;890:164352. doi: 10.1016/j.scitotenv.2023.164352, PMID 37230354
Sohrabi R, Paasch BC, Liber JA, He SY. Phyllosphere microbiome. Annu Rev Plant Biol. 2023;74:539-68. doi: 10.1146/annurev-arplant-102820-032704, PMID 36854478
Álvarez-Pérez S, Lievens B, de Vega C. Floral nectar and honeydew microbial diversity and their role in biocontrol of insect pests and pollination. Curr Opin Insect Sci. 2024;61:101138. doi: 10.1016/j. cois.2023.101138. PMID 37931689
Cullen NP, Fetters AM, Ashman TL. Integrating microbes into pollination. Curr Opin Insect Sci. 2021;44:48-54. doi: 10.1016/j. cois.2020.11.002, PMID 33248285
Narayanan Z, Glick BR. Secondary metabolites produced by plant growth-promoting bacterial endophytes. Microorganisms. 2022;10(10):2008. doi: 10.3390/microorganisms10102008, PMID 36296283
Ngalimat MS, Mohd Hata E, Zulperi D, Ismail SI, Ismail MR, Mohd Zainudin NA, et al. Plant growth-promoting bacteria as an emerging tool to manage bacterial rice pathogens. Microorganisms. 2021;9(4):682. doi: 10.3390/microorganisms9040682, PMID 33810209
Adeleke BS, Babalola OO. Pharmacological potential of fungal endophytes associated with medicinal plants: A review. J Fungi (Basel). 2021;7(2):147. doi: 10.3390/jof7020147, PMID 33671354
Koza NA, Adedayo AA, Babalola OO, Kappo AP. Microorganisms in plant growth and development: Roles in abiotic stress tolerance and secondary metabolites secretion. Microorganisms. 2022;10(8):1528. doi: 10.3390/microorganisms10081528, PMID 36013946
Todd JN, Carreón-Anguiano KG, Islas-Flores I, Canto-Canché B. Fungal effectoromics: A world in constant evolution. Int J Mol Sci. 2022;23(21):13433. doi: 10.3390/ijms232113433, PMID 36362218
Dalakouras A, Katsaouni A, Avramidou M, Dadami E, Tsiouri O, Vasileiadis S, et al. A beneficial fungal root endophyte triggers systemic RNA silencing and DNA methylation of a host reporter gene. RNA Biol. 2023;20(1):20-30. doi: 10.1080/15476286.2022.2159158, PMID 36573793
Omomowo OI, Babalola OO. Bacterial and fungal endophytes: Tiny giants with immense beneficial potential for plant growth and sustainable agricultural productivity. Microorganisms. 2019;7(11):481. doi: 10.3390/microorganisms7110481, PMID 31652843
Chaudhary P, Agri U, Chaudhary A, Kumar A, Kumar G. Endophytes and their potential in biotic stress management and crop production. Front Microbiol. 2022;13:933017. doi: 10.3389/fmicb.2022.933017, PMID 36325026
Massalha H, Korenblum E, Tholl D, Aharoni A. Small molecules below‐ground: The role of specialized metabolites in the rhizosphere. Plant J. 2017;90(4):788-807. doi: 10.1111/tpj.13543, PMID 28333395
Yi HS, Yang JW, Ryu CM. ISR meets SAR outside: Additive action of the endophyte Bacillus pumilus INR7 and the chemical inducer, benzothiadiazole, on induced resistance against bacterial spot in field-grown pepper. Front Plant Sci. 2013;4:122. doi: 10.3389/ fpls.2013.00122, PMID 23717313
Wang Y, Mostafa S, Zeng W, Jin B. Function and mechanism of jasmonic acid in plant responses to abiotic and biotic stresses. Int J Mol Sci. 2021;22(16):8568. doi: 10.3390/ijms22168568, PMID 34445272
Romera FJ, García MJ, Lucena C, Martínez-Medina A, Aparicio MA, Ramos J, et al. Induced systemic resistance (ISR) and Fe deficiency responses in dicot plants. Front Plant Sci. 2019;10:287. doi: 10.3389/ fpls.2019.00287, PMID 30915094
Fahde S, Boughribil S, Sijilmassi B, Amri A. Rhizobia: A promising source of plant growth-promoting molecules and their non-legume interactions: Examining applications and mechanisms. Agriculture. 2023;13(7):1279. doi: 10.3390/agriculture13071279
Steenhoudt O, Vanderleyden J. Azospirillum, a free-living nitrogen-fixing bacterium closely associated with grasses: Genetic, biochemical and ecological aspects. FEMS Microbiol Rev. 2000;24(4):487-506. doi: 10.1111/j.1574-6976.2000.tb00552.x, PMID 10978548
Etesami H, Jeong BR, Glick BR. Potential use of Bacillus spp. as an effective biostimulant against abiotic stresses in crops-A review. Curr Res Biotechnol. 2023;5:100128. doi: 10.1016/j. crbiot.2023.100128
Zheng M, Wang W, Hayes M, Nydell A, Tarr MA, Van Bael SA, et al. Degradation of Macondo 252 oil by endophytic Pseudomonas putida. J Environ Chem Eng. 2018;6(1):643-8. doi: 10.1016/j.jece.2017.12.071
Eid AM, Fouda A, Abdel-Rahman MA, Salem SS, Elsaied A, Oelmüller R, et al. Harnessing bacterial endophytes for promotion of plant growth and biotechnological applications: An overview. Plants (Basel). 2021;10(5):935. doi: 10.3390/plants10050935, PMID 34067154
Jangir P, Shekhawat PK, Bishnoi A, Ram H, Soni P. Role of Serendipita indica in enhancing drought tolerance in crops. Physiol Mol Plant Pathol. 2021;116:101691. doi: 10.1016/j.pmpp.2021.101691
Newman MA, Sundelin T, Nielsen JT, Erbs G, MAMP. MAMP (microbe-associated molecular pattern) triggered immunity in plants. Front Plant Sci. 2013;4:139. doi: 10.3389/fpls.2013.00139, PMID 23720666
Kumar V, Nautiyal CS. Endophytes modulate plant genes: Present status and future perspectives. Curr Microbiol. 2023;80(11):353. doi: 10.1007/s00284-023-03466-y, PMID 37740026
Wasternack C, Hause B. Jasmonates: Biosynthesis, perception, signal transduction and action in plant stress response, growth and development. An update to the 2007 review in Annals of Botany. Ann Bot. 2013;111(6):1021-58. doi: 10.1093/aob/mct067, PMID 23558912
Rebouh NY, Khugaev CV, Utkina AO, Isaev KV, Mohamed ES, Kucher DE. Contribution of eco-friendly agricultural practices in improving and stabilizing wheat crop yield: A review. Agronomy. 2023;13(9):2400. doi: 10.3390/agronomy13092400
Tsipinana S, Husseiny S, Alayande KA, Raslan M, Amoo S, Adeleke R. Contribution of endophytes towards improving plant bioactive metabolites: A rescue option against red-taping of medicinal plants. Front Plant Sci. 2023;14:1248319. doi: 10.3389/fpls.2023.1248319, PMID 37771494
Vélëz H, Gauchan DP, García-Gil MD. Taxol and β-tubulins from endophytic fungi isolated from the Himalayan Yew, Taxus wallichiana Zucc. Front Microbiol. 2022;13:956855. doi: 10.3389/ fmicb.2022.956855, PMID 36246258
Zhang J, Zang S, Bai B, Fan S. Isolation and screening for limonin-producing endophytic bacteria from Citrus maxima (Burm.) Merr. cv. Shatian Yu. Biotechnol Appl Biochem. 2019;66(2):192-201. doi: 10.1002/bab.1721, PMID 30578642
Yang Y, Zhao H, Barrero RA, Zhang B, Sun G, Wilson IW, et al. Genome sequencing and analysis of the paclitaxel-producing endophytic fungus Penicillium aurantiogriseum NRRL 62431. BMC Genomics. 2014;15:69. doi: 10.1186/1471-2164-15-69, PMID 24460898
Zaiyou J, Li M, Xiqiao H. An endophytic fungus efficiently producing paclitaxel isolated from Taxus wallichiana var. mairei. Medicine (Baltimore). 2017;96(27):e7406. doi: 10.1097/MD.0000000000007406, PMID 28682896
Kang MK, Kim JH, Liu MJ, Jin CZ, Park DJ, Kim J, et al. New discovery on the nematode activity of aureothin and alloaureothin isolated from endophytic bacteria Streptomyces sp. AE170020. Sci Rep. 2022;12(1):3947. doi: 10.1038/s41598-022-07879-w, PMID 35273247
Zotchev SB. Unlocking the potential of bacterial endophytes from medicinal plants for drug discovery. Microb Biotechnol. 2024;17(2):e14382. doi: 10.1111/1751-7915.14382, PMID 38345183
Um S, Lee J, Kim SH. Lobophorin producing endophytic Streptomyces olivaceus JB1 associated with Maesa japonica (Thunb.) Moritzi & Zoll. Front Microbiol. 2022;13:881253. doi: 10.3389/fmicb.2022.881253, PMID 35572656.
Robinson SL, Panaccione DG. Diversification of ergot alkaloids in natural and modified fungi. Toxins (Basel). 2015;7(1):201-18. doi: 10.3390/toxins7010201, PMID 25609183.
Eldeghidy A, Abdel-Fattah G, El-Sayed AS, Abdel-Fattah GG. Production, bioprocessing and antiproliferative activity of camptothecin from Aspergillus terreus, endophyte of Cinnamomum camphora: restoring their biosynthesis by indigenous microbiome of C. camphora. Microb Cell Fact. 2023;22(1):143. doi: 10.1186/s12934-023-02158-3, PMID 37533061
Pu X, Chen F, Yang Y, Qu X, Zhang G, Luo Y. Isolation and characterization of Paenibacillus polymyxa LY214, a camptothecin-producing endophytic bacterium from Camptotheca acuminata. J Ind Microbiol Biotechnol. 2015;42(8):1197-202. doi: 10.1007/s10295-015- 1643-4, PMID 26124076
O A, Nagadesi PK. Endophytic, non-endophytic fungal alkaloids and its applications. Saudi J Pathol Microbiol. 2022;7(1):4-19. doi: 10.36348/ sjpm.2022.v07i01.002
Ding G, Song YC, Chen JR, Xu C, Ge HM, Wang XT, et al. Chaetoglobosin U, a cytochalasan alkaloid from endophytic Chaetomium globosum IFB-E019. J Nat Prod. 2006;69(2):302-4. doi: 10.1021/np050515+, PMID 16499339
Koul M, Lakra NS, Chandra R, Chandra S. Catharanthus roseus and prospects of its endophytes: A new avenue for production of bioactive metabolites. Int J Pharm Sci Res. 2013;4(7):2705-16.
Birat K, Binsuwaidan R, Siddiqi TO, Mir SR, Alshammari N, Adnan M, et al. Report on vincristine-producing endophytic fungus nigrospora zimmermanii from leaves of Catharanthus roseus. Metabolites. 2022;12(11):1119. doi: 10.3390/metabo12111119, PMID 36422259
Kovalev MA, Gladysh NS, Bogdanova AS, Bolsheva NL, Popchenko MI, Kudryavtseva AV. Editing metabolism, sex, and microbiome: How can we help poplar resist pathogens? Int J Mol Sci. 2024;25(2):1308. doi: 10.3390/ijms25021308, PMID 38279306
Singh A, Singh DK, Kharwar RN, White JF, Gond SK. Fungal endophytes as efficient sources of plant-derived bioactive compounds and their prospective applications in natural product drug discovery: Insights, avenues, and challenges. Microorganisms. 2021;9(1):197. doi: 10.3390/microorganisms9010197, PMID 33477910
Wang L, Chen M, Lam PY, Dini-Andreote F, Dai L, Wei Z. Multifaceted roles of flavonoids mediating plant-microbe interactions. Microbiome. 2022;10(1):233. doi: 10.1186/s40168- 022-01420-x, PMID 36527160
Seetharaman P, Gnanasekar S, Chandrasekaran R, Chandrakasan G, Kadarkarai M, Sivaperumal S. Isolation and characterization of anticancer flavone chrysin (5,7-dihydroxy flavone)-producing endophytic fungi from Passiflora incarnata L. leaves. Ann Microbiol. 2017;67(4):321-31. doi: 10.1007/s13213-017-1263-5
Priyanka GD, Shobha SS, Shruthi SD. Phytochemical analysis and molecular characterization of Moringa oleifera and its endophytic fungi. Int J Pharm Pharm Sci. 2023;15(4):39-46. doi: 10.22159/ ijpps.2023v15i4.47020
Donga S, Moteriya P, Chanda S. Evaluation of antimicrobial and synergistic antimicrobial properties of Pterocarpus santalinus. Asian J Pharm Clin Res. 2017;10(11):204. doi: 10.22159/ajpcr.2017. v10i11.20939
Erlianda D, Rizal MF, Budiardjo SB. Antibacterial effect of flavonoids from propolis produced by Trigona on atpase activity of streptococcus mutans. Int J Appl Pharm. 2018;9:6-9. doi: 10.22159/ ijap.2017.v9s2.02
Abo-Kadoum MA, Abouelela ME, Al Mousa AA, Abo-Dahab NF, Mosa MA, Helmy YA, et al. Resveratrol biosynthesis, optimization, induction, bio-transformation and bio-degradation in mycoendophytes. Front Microbiol. 2022;13:1010332. doi: 10.3389/ fmicb.2022.1010332, PMID 36304949
Nongkhlaw FM, Joshi SR. Horizontal gene transfer of the non-ribosomal peptide synthetase gene among endophytic and epiphytic bacteria associated with ethnomedicinal plants. Curr Microbiol. 2016;72(1):1-11. doi: 10.1007/s00284-015-0910-y, PMID 26362160
Castillo UF, Strobel GA, Ford EJ, Hess WM, Porter H, Jensen JB, et al. Munumbicins, wide-spectrum antibiotics produced by Streptomyces NRRL 30562, endophytic on Kennedia nigriscans. Microbiology (Reading). 2002;148(9):2675-85. doi: 10.1099/00221287-148-9- 2675, PMID 12213914
Mülner P, Schwarz E, Dietel K, Herfort S, Jähne J, Lasch P, et al. Fusaricidins, polymyxins and volatiles produced by Paenibacillus polymyxa strains DSM 32871 and M1. Pathogens. 2021;10(11):1485. doi: 10.3390/pathogens10111485, PMID 34832640
Karwasara VS, Dixit VK. Culture medium optimization for camptothecin production in cell suspension cultures of Nothapodytes nimmoniana (J. Grah.) Mabberley. Plant Biotechnol Rep. 2013;7(3):357-69. doi: 10.1007/s11816-012-0270-z
Shweta S, Zuehlke S, Ramesha BT, Priti V, Mohana Kumar P, Ravikanth G, et al. Endophytic fungal strains of Fusarium solani, from Apodytes dimidiata E. Mey. ex Arn (Icacinaceae) produce camptothecin, 10-hydroxycamptothecin and 9-methoxycamptothecin. Phytochemistry. 2010;71(1):117-22. doi: 10.1016/j.phytochem.2009.09.030, PMID 19863979
Rehman S, Shawl AS, Verma V, Kour A, Athar M, Andrabi R, et al. An endophytic Neurospora sp. from Nothapodytes foetida producing camptothecin. Prikl Biokhim Mikrobiol. 2008;44(2):225-31. doi: 10.1134/S0003683808020130, PMID 18669267
Pu X, Qu X, Chen F, Bao J, Zhang G, Luo Y. Camptothecin-producing endophytic fungus Trichoderma atroviride LY357: Isolation, identification, and fermentation conditions optimization for camptothecin production. Appl Microbiol Biotechnol. 2013;97(21):9365-75. doi: 10.1007/s00253-013-5163-8, PMID 23949997
Zhang Y, Han T, Ming Q, Wu L, Rahman K, Qin L. Alkaloids produced by endophytic fungi: A review. Nat Prod Commun. 2012;7(7):963-8. doi: 10.1177/1934578X1200700742, PMID 22908594
Wang Y, Xu L, Ren W, Zhao D, Zhu Y, Wu X. Bioactive metabolites from Chaetomium globosum L18, an endophytic fungus in the medicinal plant Curcuma wenyujin. Phytomedicine. 2012;19(3- 4):364-8. doi: 10.1016/j.phymed.2011.10.011, PMID 22112725
Li JY, Strobel G, Sidhu R, Hess WM, Ford EJ. Endophytic Taxol-producing fungi from bald cypress, Taxodium distichum. Microbiology(Reading). 1996;142(8):2223-6. doi: 10.1099/13500872-142-8- 2223, PMID 8760934
Ismaiel AA, Ahmed AS, Hassan IA, El-Sayed ER, Karam El-Din AA. Production of paclitaxel with anticancer activity by two local fungal endophytes, Aspergillus fumigatus and Alternaria tenuissima. Appl Microbiol Biotechnol. 2017;101(14):5831-46. doi: 10.1007/ s00253-017-8354-x, PMID 28612104
Adhikari P, Singh M, Pandey A. Production of Taxol by endophytic fungi isolated from roots of Himalayan yew (Taxus wallichiana Zucc.). J Graph Era Univ. 2023;10:195-216. doi: 10.13052/jgeu0975- 1416.1028
Pathirana CK, Madhujith T, Eeswara J. Bael (Aegle marmelos L. Corrêa), a medicinal tree with immense economic potentials. Adv Agric. 2020;2020:1-13. doi: 10.1155/2020/8814018
Zhang P, Zhou PP, Yu LJ. An endophytic Taxol-producing fungus from Taxus media, Cladosporium cladosporioides MD2. Curr Microbiol. 2009;59(3):227-32. doi: 10.1007/s00284-008-9270-1, PMID 19484305
Jam Ashkezari S, Fotouhifar KB. Diversity of endophytic fungi of common yew (Taxus baccata L.) in Iran. Mycol Progress. 2017;16(3):247-56. doi: 10.1007/s11557-017-1274-4
Liu AR, Xu T, Guo LD. Molecular and morphological description of Pestalotiopsis hainanensis sp. nov., a new endophyte from a tropical region of China. Fungal Divers. 2007;24:23-36.
Gangadevi V, Muthumary J. Taxol production by Pestalotiopsis terminaliae, an endophytic fungus of Terminalia arjuna (Arjun tree). Biotechnol Appl Biochem. 2009;52(1):9-15. doi: 10.1042/ BA20070243, PMID 18254723
Wang J, Li G, Lu H, Zheng Z, Huang Y, Su W. Taxol from Tubercularia sp. strain TF5, an endophytic fungus of Taxus mairei. FEMS Microbiol Lett. 2000;193(2):249-53. doi: 10.1111/j.1574- 6968.2000.tb09432.x, PMID 11111032
Kour A, Shawl AS, Rehman S, Sultan P, Qazi PH, Suden P, et al. Isolation and identification of an endophytic strain of Fusarium oxysporum producing podophyllotoxin from Juniperus recurva. World J Microbiol Biotechnol. 2008;24(7):1115-21. doi: 10.1007/ s11274-007-9582-5
Jayanthi G, Karthikeyan K, Muthumary J. Isolation and characterization of anticancer compound, Taxol from an endophytic fungus Phomopsis longicolla. Int J Curr Res. 2015;7:12727-34.
Almatar M, Makky EA. Chemotherapeutic agents: Taxol and vincristine isolated from endophytic fungi. Int J Curr Pharm Res. 2015;6:80-8.
Fill TP, da Silva BF, Rodrigues-Fo E. Biosynthesis of phenylpropanoid amides by an endophytic Penicillium brasilianum found in root bark of Melia azedarach. J Microbiol Biotechnol. 2010;20(3):622-9. PMID 20372037
Zhao J, Zhou L, Wang J, Shan T, Zhong L, Liu X, et al. Endophytic Fungi for Producing Bioactive Compounds Originally from their Plants, Host. Badajoz: Formatex Research Center; 2010. p. 567-76.
Uzma F, Mohan CD, Hashem A, Konappa NM, Rangappa S, Kamath PV, et al. Endophytic fungi-alternative sources of cytotoxic compounds: A review. Front Pharmacol. 2018;9:309. doi: 10.3389/ fphar.2018.00309, PMID 29755344
Huang JX, Zhang J, Zhang XR, Zhang K, Zhang X, He XR. Mucor fragilis as a novel source of the key pharmaceutical agents podophyllotoxin and kaempferol. Pharm Biol. 2014;52(10):1237-43. doi: 10.3109/13880209.2014.885061, PMID 24863281
Eyberger AL, Dondapati R, Porter JR. Endophyte fungal isolates from Podophyllum peltatum produce podophyllotoxin. J Nat Prod. 2006;69(8):1121-4. doi: 10.1021/np060174f, PMID 16933860
Biswas D, Biswas P, Nandy S, Mukherjee A, Pandey DK, Dey A. Endophytes producing podophyllotoxin from Podophyllum sp. and other plants: A review on isolation, extraction and bottlenecks. S Afr J Bot. 2020;134:303-13. doi: 10.1016/j.sajb.2020.02.038
Thi Tran H, Thu Nguyen G, Thi Nguyen HH, Thi Tran H, Hong Tran Q, Ho Tran Q, et al. Isolation and cytotoxic potency of endophytic fungi associated with Dysosma difformis, a study for the Novel Resources of Podophyllotoxin. Mycobiology. 2022;50(5):389-98. doi: 10.1080/12298093.2022.2126166, PMID 36404896
Yousefzadi M, Sharifi M, Behmanesh M, Moyano E, Bonfill M, Cusido RM, et al. Podophyllotoxin: Current approaches to its biotechnological production and future challenges. Eng Life Sci. 2010;10(4):281-92. doi: 10.1002/elsc.201000027
Kumar A, Patil D, Rajamohanan PR, Ahmad A. Isolation, purification and characterization of vinblastine and vincristine from endophytic fungus Fusarium oxysporum isolated from Catharanthus roseus. PLoS One. 2013;8(9):e71805. doi: 10.1371/journal.pone.0071805, PMID 24066024
Kuncharoen N, Bunbamrung N, Intaraudom C, Choowong W, Thawai C, Tanasupawat S, et al. Antimalarial and antimicrobial substances isolated from the endophytic actinomycete, Streptomyces aculeolatus MS1-6. Phytochemistry. 2023;207:113568. doi: 10.1016/j.phytochem.2022.113568, PMID 36565946
Ezra D, Castillo UF, Strobel GA, Hess WM, Porter H, Jensen JB, et al. Coronamycins, peptide antibiotics produced by a verticillate Streptomyces sp. (MSU-2110) endophytic on Monstera sp. Microbiology (Reading). 2004;150(4):785-93. doi: 10.1099/ mic.0.26645-0, PMID 15073289
Yang A, Zeng S, Yu L, He M, Yang Y, Zhao X, et al. Characterization and antifungal activity against Pestalotiopsis of a fusaricidin-type compound produced by Paenibacillus polymyxa Y-1. Pestic Biochem Physiol. 2018;147:67-74. doi: 10.1016/j.pestbp.2017.08.012, PMID 29933995
Yang YH, Yang DS, Li GH, Liu R, Huang XW, Zhang KQ, et al. New secondary metabolites from an engineering mutant of endophytic Streptomyces sp. CS. Fitoterapia. 2018;130:17-25. doi: 10.1016/j. fitote.2018.07.019, PMID 30076887
Zhu Y, Kong Y, Hong Y, Zhang L, Li S, Hou S, et al. Huoshanmycins A-C, new polyketide dimers produced by endophytic Streptomyces sp. HS-3-L-1 from Dendrobium huoshanense. Front Chem. 2021;9:807508. doi: 10.3389/fchem.2021.807508, PMID 35237566
Bekiesch P, Oberhofer M, Sykora C, Urban E, Zotchev SB. Piperazic acid containing peptides produced by an endophytic Streptomyces sp. isolated from the medicinal plant Atropa belladonna. Nat Prod Res. 2021;35(7):1090-6. doi: 10.1080/14786419.2019.1639174, PMID 31303055
Zhang C, Fan L, Fan S, Wang J, Luo T, Tang Y, et al. Cinnamomum cassia Presl: A review of its traditional uses, phytochemistry, pharmacology and toxicology. Molecules. 2019;24(19):3473. doi: 10.3390/molecules24193473, PMID 31557828
Wang W, Kim S, Vu TH, Quach NT, Oh E, Park KH, et al. Bioactive piperazic acid-bearing cyclodepsipeptides, Lydiamycins E-H, from an Endophytic Streptomyces sp. Associated with Cinnamomum cassia. J Nat Prod. 2023;86(4):751-8. doi: 10.1021/acs.jnatprod.2c00902, PMID 36812487
Shang NN, Zhang Z, Huang JP, Wang L, Luo J, Yang J, et al. Glycosylated piericidins from an endophytic Streptomyces with cytotoxicity and antimicrobial activity. J Antibiot (Tokyo). 2018;71(7):672-6. doi: 10.1038/s41429-018-0051-1, PMID 29651143
Kim N, Shin JC, Kim W, Hwang BY, Kim BS, Hong YS, et al. Cytotoxic 6-alkylsalicylic acids from the endophytic Streptomyces laceyi. J Antibiot (Tokyo). 2006;59(12):797-800. doi: 10.1038/ ja.2006.105, PMID 17323647
Ding L, Maier A, Fiebig HH, Lin WH, Hertweck C. A family of multicyclic indolosesquiterpenes from a bacterial endophyte. Org Biomol Chem. 2011;9(11):4029-31. doi: 10.1039/c1ob05283g, PMID 21528153
Ding L, Münch J, Goerls H, Maier A, Fiebig HH, Lin WH, et al. Xiamycin, a pentacyclic indolosesquiterpene with selective anti- HIV activity from a bacterial mangrove endophyte. Bioorg Med Chem Lett. 2010;20(22):6685-7. doi: 10.1016/j.bmcl.2010.09.010, PMID 20880706
Rahman MM, Ishtiaque GM, Rahat SA, Hossain MA, Islam MR, Maeesa SK, et al. Multifunctional role of natural products for therapeutic approaches of prostate cancer: an updated review. J Herb Med. 2023;42:100803. doi: 10.1016/j.hermed.2023.100803
Nawara HM, Afify SM, Hassan G, Zahra MH, Seno A, Seno M. Paclitaxel-based chemotherapy targeting cancer stem cells from mono-to combination therapy. Biomedicines. 2021;9(5):500. doi: 10.3390/biomedicines9050500, PMID 34063205
Liu WC, Gong T, Zhu P. Advances in exploring alternative Taxol sources. RSC Adv. 2016;6(54):48800-9. doi: 10.1039/C6RA06640B
Swamy MK, Das T, Nandy S, Mukherjee A, Pandey DK, Dey A. Endophytes for the production of anticancer drug, paclitaxel. In: Paclitaxel. Netherlands: Elsevier; 2022. p. 203-28. doi: 10.1016/ B978-0-323-90951-8.00012-6
Banadka A, Narasimha SW, Dandin VS, Naik PM, Vennapusa AR, Melmaiee K, et al. Biotechnological approaches for the production of camptothecin. Appl Microbiol Biotechnol. 2024;108(1):382. doi: 10.1007/s00253-024-13187-2, PMID 38896329
Sonowal S, Gogoi U, Buragohain K, Nath R. Endophytic fungias a potential source of anti-cancer drug. Arch Microbiol. 2024;206(3):122. doi: 10.1007/s00203-024-03829-4, PMID 38407579
Singh N, Agrawal P. A comprehensive review on the pharmacognostic and toxicological profile of Podophyllum peltatum (Bajiaolian). Pharmacol Res Mod Chin Med. 2024;10:100353. doi: 10.1016/j. prmcm.2023.100353
Kao WF, Hung DZ, Tsai WJ, Lin KP, Deng JF. Podophyllotoxin intoxication: toxic effect of Bajiaolian in herbal therapeutics. Hum Exp Toxicol. 1992;11(6):480-7. doi: 10.1177/096032719201100607, PMID 1361136
Zhang X, Rakesh KP, Shantharam CS, Manukumar HM, Asiri AM, Marwani HM, et al. Podophyllotoxin derivatives as an excellent anticancer aspirant for future chemotherapy: A key current imminent needs. Bioorg Med Chem. 2018;26(2):340-55. doi: 10.1016/j. bmc.2017.11.026
Tiwari P, Bae H. Endophytic fungi: Key insights, emerging prospects, and challenges in natural product drug discovery. Microorganisms. 2022;10(2):360. doi: 10.3390/microorganisms10020360, PMID 35208814
Li J, Sun H, Jin L, Cao W, Zhang J, Guo CY, et al. Alleviation of podophyllotoxin toxicity using coexisting flavonoids from Dysosma versipellis. PLOS One. 2013;8(8):e72099. doi: 10.1371/journal. pone.0072099. PMID 23991049
Kumar A, Ahmad A. Biotransformation of vinblastine to vincristine by the endophytic fungus Fusarium oxysporum isolated from Catharanthus roseus. Biocatal Biotransform. 2013;31(2):89-93. doi: 10.3109/10242422.2013.776544
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