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Sains
Malaysiana 55(8)(2026): 1324-1336
http://doi.org/10.17576/jsm-2026-5508-08
Harnessing
Rubiaceae Plant Endophytic Fungi: A Comprehensive Review of Novel Antimicrobial
Compounds for Drug Discovery
(Memanfaatkan
Kulat Endofitik Tumbuhan Rubiaceae: Ulasan Komprehensif Sebatian Antimikrob
Baharu untuk Penemuan Ubat)
INHERNI MARTI ABNA1,2,*, MARLIA SINGGIH
WIBOWO1, IRDA FIDRIANNY1 & ANDRIA AGUSTA3
1School of Pharmacy, Bandung Institute of Technology, Jl.
Ganesa 10, Bandung, West Java 40132, Indonesia
2Pharmacy Study Program, Faculty of Health Sciences,
Universitas Esa Unggul, Jl. Arjuna Utara No.9, Duri Kepa, Kebon Jeruk
Sub-District, West Jakarta City, Special Capital Region of Jakarta 11510,
Indonesia
3Research Center for Pharmaceutical Ingredients and
Traditional Medicine, National Research and Innovation Agency, Jl. Raya
Jakarta-Bogor Km. 46, Cibinong, West Java 16915, Indonesia
Diserahkan:
26 November 2025/Diterima: 5 Ogos 2026
Abstract
Antimicrobial resistance (AMR)
continues to threaten the effectiveness of existing therapies, driving the
urgent search for novel therapeutic leads from nature. Rubiaceae
plant-associated endophytic fungi are increasingly recognized as valuable
producers of structurally diverse secondary metabolites with antibacterial,
antifungal, and antimycobacterial activities. Unlike previous reviews that
primarily focus on bioactive compounds, this narrative-critical review
integrates ecological factors influencing endophytic diversity with advanced
strategies to awaken cryptic biosynthetic pathways. We systematically evaluate
approaches including One Strain-Many Compounds (OSMAC), co-culture, chemical
and epigenetic elicitation, genome-guided discovery, and heterologous
expression. Furthermore, this review critically analyzes pharmacological
metrics, specifically minimum inhibitory concentration (MIC), cytotoxicity,
Selectivity Index (SI), mechanisms of action, and the potential of fungal
metabolites as antibiotic adjuvants. Current evidence suggests that the
clinical development of these natural products is constrained by methodological
inconsistencies, a lack of animal model testing, insufficient pharmacokinetic
profiling, and large-scale manufacturing hurdles. Future progress in drug
discovery will heavily depend on adopting standardized evaluation criteria and
comprehensive pharmacological screening to successfully transform these endophytic
metabolites into viable clinical candidates.
Keywords: Antimicrobial secondary
metabolites; drug discovery; endophytic fungi; OSMAC; Rubiaceae; selectivity
index
Abstrak
Kerintangan antimikrob (AMR) terus
mengancam keberkesanan terapi sedia ada, sekali gus mendorong pencarian segera
untuk terapeutik baharu daripada alam semula jadi. Kulat endofit yang berkaitan
dengan tumbuhan famili Rubiaceae semakin dikenali sebagai pengeluar pelbagai
metabolit sekunder yang memiliki aktiviti antibakteria, antikulat dan
antimikobakteria. Tidak seperti ulasan terdahulu yang sebahagian besarnya
tertumpu kepada sebatian bioaktif, ulasan ini menggabungkan faktor ekologi yang
mempengaruhi kepelbagaian endofit dengan strategi lanjutan untuk meningkatkan
laluan biosintetik yang masih samar. Kami menilai pelbagai pendekatan secara
sistematik termasuk Satu Strain-Banyak Sebatian (OSMAC), kultur bersama,
elisitasi kimia dan epigenetik, penemuan berpandukan genom dan pengekspresan
heterolog. Tambahan pula, ulasan ini menganalisis secara kritis metrik
farmakologi, khususnya kepekatan perencatan minimum (MIC), kesitotoksikan,
Indeks Kepilihan (SI), mekanisme tindakan dan potensi metabolit kulat sebagai
adjuvan antibiotik. Bukti semasa mencadangkan bahawa pembangunan klinikal
produk semula jadi ini masih dikekang oleh ketidakseragaman metodologi,
kekurangan ujian model haiwan, pemprofilan farmakokinetik yang tidak mencukupi
dan halangan pembuatan berskala besar. Kemajuan pada masa hadapan dalam
penemuan ubat akan sangat bergantung kepada penerapan kriteria penilaian piawai
dan penyaringan farmakologi yang komprehensif untuk berjaya mentransformasikan
metabolit endofit ini menjadi calon klinikal yang berdaya maju.
Kata kunci:
Indeks keselektifan; kulat endofit; metabolit sekunder antimikrob; OSMAC;
penemuan ubat; Rubiaceae
RUJUKAN
Agustina, I., Lay, C.S., Astuti, P. &
Hertiani, T. 2024. Cytotoxicity screening of endophytic fungi from Phaleria
macrocarpa (Scheff.) Boerl collected in Yogyakarta District. Indonesian
Journal of Pharmacy 35(2): 219-226. https://doi.org/10.22146/ijp.7415
Aniceto, N., Freitas, A. & Ghafourian, T.
2026. Modeling ADME/Tox for drug discovery in the age of data. Springer
Handbook of Chem- and Bioinformatics. Cham: Springer. pp. 387-415. https://doi.org/10.1007/978-3-031-81728-1_18
Atanasov, A.G., Zotchev, S.B., Dirsch, V.M.
& Supuran, C.T. 2021. Natural products in drug discovery: Advances and
opportunities. Nature Reviews Drug Discovery 20: 200-216. https://doi.org/10.1038/s41573-020-00114-z
Bansal, S., Joshi, M., Mahajan, P., Sharma, S.,
Kaur, S., Thakur, B., Jassal, P.S., Singh, R. & Tripathi, M. 2025.
Endophytic fungi as a source of antimicrobial compounds against emerging
methicillin-resistant Staphylococcus aureus. Mycology 17(1):
2531886. https://doi.org/10.1080/21501203.2025.2531886
Bertrand, S., Bohni, N., Schnee, S., Schumpp,
O., Gindro, K. & Wolfender, J-L. 2014. Metabolite induction via
microorganism co-culture: A potential way to enhance chemical diversity for
drug discovery. Biotechnology Advances 32(6): 1180-1204. https://doi.org/10.1016/j.biotechadv.2014.03.001
Bhavnani, S.M., Krause, K.M. & Ambrose,
P.G. 2020. A broken antibiotic market: Review of strategies to incentivize drug
development. Open Forum Infectious Diseases 7(7): ofaa083. https://doi.org/10.1093/ofid/ofaa083
Calvo-Gomez, O., Eshboev, F. & Mullaiarova,
K. 2025. Endophytic bioactive compounds for wound healing: A review of
biological activities and therapeutic potential. Microorganism 13(7):
1691. https://doi.org/10.3390/microorganisms13071691
Caruso, D.J., Palombo, E.A., Moulton, S.E.
& Zaferanloo, B. 2022. Exploring the promise of endophytic fungi: A review
of novel antimicrobial compounds. Microorganisms 10(10): 1990. https://doi.org/10.3390/microorganisms10101990
Castillo-González, H. & Slot, J.C. 2025.
Exploring Rubiaceae fungal endophytes across contrasting tropical forests, tree
tissues, and developmental stages. Peer Community Journal 5: e33. https://doi.org/10.24072/pcjournal.526
Chandra, H., Yadav, A., Prasad, R., Jeet, S.,
Kalra, S.J., Singh, A., Bhardwaj, N. & Kumar, K. 2024. Fungal endophytes
from medicinal plants acting as natural therapeutic reservoir. Current
Research in Microbial Sciences 3: 100146. https://doi.org/10.22541/au.169217917.78306347/v1
Chen, S., Li, H., Chen, Y., Li, S., Xu, J.,
Guo, H., Liu, Z., Zhu, S., Liu, H. & Zhang, W. 2019. Three new diterpenes
and two new sesquiterpenoids from the endophytic fungus Trichoderma
koningiopsis A729. Bioorganic Chemistry 87: 669-674. https://doi.org/10.1016/j.bioorg.2019.02.005
Chen, Y., Hu, B., Xing, J. & Li, C. 2021.
Endophytes: The novel sources for plant terpenoid biosynthesis. Applied
Microbiology and Biotechnology 105(12): 4501-4513. https://doi.org/10.1007/s00253-021-11350-7
Christian, N., Sedio, B.E., Florez-Buitrago,
X., Ramirez-Camejo, L.A., Rojas, E.I., Mejia, L.C., Palmedo, S.K.,
Alvarez-Manjarrez, J. & Basic, N. 2020. Host affinity of endophytic fungi
and the potential for reciprocal interactions involving host secondary
chemistry. American Journal of Botany 107(2): 219-228. https://doi.org/10.1002/ajb2.1436
Clinical and Laboratory Standards Institute
(CLSI). 2026. Performance Standards for Antimicrobial Susceptibility Testing.
36th ed. Wayne: CLSI.
Cos, P., Vlietinck, A.J., Vanden Berghe, D.
& Maes, L. 2006. Anti-infective potential of natural products: How to
develop a stronger in vitro 'proof-of-concept'. Journal of
Ethnopharmacology 106(3): 290-302. https://doi.org/10.1016/j.jep.2006.04.003
Cruz, J.S., da Silva, C.A. & Hamerski, L.
2020. Natural products from endophytic fungi associated with Rubiaceae species. Journal of Fungi 6(3): 128. https://doi.org/10.3390/jof6030128
de Oliveira, L.C., Da Costa, W.C.L., Vinagre,
V.G., Siqueira, J.E.D.S., Silva, S.D.C., Silva, S.Y.S., De Souza, C.R.B. &
Marinho, A.M.D.R. 2022. Bioprospecting the antibacterial activity of endophytic
fungi from Noni (Morinda citrifolia) against bacterial spot of the
passion fruit tree. Agronomy 12(7): 1690. https://doi.org/10.3390/agronomy12071690
de Sena Filho, J.G., Quin, M.B., Spakowicz,
D.J., Shaw, J.J., Kucera, K., Dunican, B., Strobel, S.A. & Schmidt-Dannert,
C. 2016. Genome of Diaporthe sp. provides insights into the potential
inter-phylum transfer of a fungal sesquiterpenoid biosynthetic pathway. Fungal
Biology 120(8): 1050-1063. https://doi.org/10.1016/j.funbio.2016.04.001
Dos Reis, J.B.A., Lorenzi, A.S. & Vale,
H.M.M. 2022. Methods used for the study of endophytic fungi: A review on
methodologies and challenges, and associated tips. Archives of Microbiology 204(11): 675. https://doi.org/10.1007/s00203-022-03283-0
Durán-Iturbide, N.A., Díaz-Eufracio, B.I. &
Medina-Franco, J.L. 2020. In silico ADME/Tox profiling of natural
products: A focus on BIOFACQUIM. ACS Omega 5(26): 16076-16084. https://doi.org/10.1021/acsomega.0c01581
Escudero-Leyva, E., Granados-Montero, M.M.,
Orozco-Ortiz, C., Araya-Valverde, E., Alvarado-Picado, E., Chaves-Fallas, J.M.,
Aldrich-Wolfe, L. & Chaverri, P. 2023. The endophytobiome of wild Rubiaceae
as a source of antagonistic fungi against the American leaf spot of coffee (Mycena
citricolor). Journal of Applied Microbiology 134(5): lxad090. https://doi.org/10.1093/jambio/lxad090
Eshboev, F., Mamadalieva, N., Nazarov, P.A.,
Hussain, H., Katanaev, V., Egamberdieva, D. & Azimova, S. 2024.
Antimicrobial action mechanisms of natural compounds isolated from endophytic
microorganisms. Antibiotics 13(3): 271. https://doi.org/10.3390/antibiotics13030271
European Committee on Antimicrobial
Susceptibility Testing (EUCAST). 2026. Breakpoint Tables for Interpretation
of MICs and Zone Diameters. Version 16.0.
Gakuubi, M.M., Ching, K.C., Munusamy, M.,
Wibowo, M., Liang, Z.X., Kanagasundaram, Y. & Ng, S.B. 2022. Enhancing the
discovery of bioactive secondary metabolites from fungal endophytes using
chemical elicitation and variation of fermentation media. Frontiers in
Microbiology 13: 898976. https://doi.org/10.3389/fmicb.2022.898976
Ganeshan, M., Arumugam, K., Veeranan-Karmegam,
R., Jayaraman, P., Chidambaram, R. & Ramalingam, S. 2021. Scaling-up
production of plant endophytes in bioreactors: Concepts, challenges, and
perspectives. Bioresources and Bioprocessing 8(1): 63. https://doi.org/10.1186/s40643-021-00417-y
Gao, Y., Xu, Y., Dong, Z., Guo, Y., Luo, J.,
Wang, F. & Yan, L. 2025. Endophytic fungal diversity and its interaction
mechanism with medicinal plants. Molecules 30(5): 1028. https://doi.org/10.3390/molecules30051028
Geistodt-Kiener, A., Chrisologue, J., Vergne,
J., Sakai, K., Ouazzani, J., Viaud, M. & O'Connell, R.J. 2023. Yeast-based
heterologous production of the colletochlorin family of fungal secondary
metabolites. Synthetic Biology 80: 216-231. https://doi.org/10.1016/j.ymben.2023.10.002
Gonzalez-Pastor, R., Carrera-Pacheco, S.E.,
Zúñiga-Miranda, J., Rodríguez-Pólit, C., Mayorga-Ramos, A., Guamán, L.P. &
Barba-Ostria, C. 2023. Current landscape of methods to evaluate antimicrobial
activity of natural extracts. Molecules 28(3): 1068. https://doi.org/10.3390/molecules28031068
Gouda, S., Das, G., Sen, S.K. & Shin, H-S.
2016. Endophytes: A treasure house of bioactive compounds of medicinal
importance. Frontiers in Microbiology 7: 1538. https://doi.org/10.3389/fmicb.2016.01538
Gubiani, J.R., Zeraik, M.L., Oliveira, C.M.,
Ximenes, V.F., Fonseca, L.M., Silva, D.H.S., Bolzani, V.S. & Araujo, A.R.
2014. Biologically active eremophilane-type sesquiterpenes from Camarops sp., an endophytic fungus isolated from Alibertia macrophylla. Journal
of Natural Products 77(11): 2419-2425. https://doi.org/10.1021/np400825s
Habjan, E., Schouten, G.K., Speer, A., van
Ulsen, P. & Bitter, W. 2024. Diving into drug-screening: Zebrafish embryos
as an in vivo platform for antimicrobial drug discovery and assessment. FEMS
Microbiology Reviews 48(3): fuae011. https://doi.org/10.1093/femsre/fuae011
Hashem, A.H., Attia, M.S., Kandil, E.K., Fawzi,
M.M., Abdelrahman, A.S., Khader, M.S., Khodaira, M.A., Emam, A.E. & Goma,
M.A. 2023. Bioactive compounds and biomedical applications of endophytic fungi:
A recent review. Journal of Fungi 9(7): 742. https://doi.org/10.1186/s12934-023-02118-x
He, Z.H., Zhang, C.L., Zhang, X., Peng, J.B.
& Ma, A.J. 2017. Spiroaspertrione A, a bridged spirocyclic meroterpenoid,
as a potent potentiator of oxacillin against methicillin-resistant Staphylococcus
aureus from Aspergillus sp. TJ23. Journal of Organic Chemistry 82(6): 3125-3131. https://doi.org/10.1021/acs.joc.7b00056
Hoyos, L.V., Vasquez-Muñoz, L.E., Osorio, Y.,
Valencia-Revelo, D., Devia-Cometa, D., Große, M., Charria-Girón, E. &
Caicedo-Ortega, N.H. 2024. Tailored culture strategies to promote antimicrobial
secondary metabolite production in Diaporthe caliensis: A metabolomic
approach. Microbial Cell Factories 23: 328. https://doi.org/10.1186/s12934-024-02567-y
Jha, P., Kaur, T., Chhabra, I., Panja, A.,
Paul, S., Kumar, V. & Malik, T. 2023. Endophytic fungi: Hidden treasure
chest of antimicrobial metabolites interrelationship of endophytes and
metabolites. Frontiers in Microbiology 14: 1227830. https://doi.org/10.3389/fmicb.2023.1227830
Kavanagh, A., Ramu, S., Gong, Y., Cooper, M.A.
& Blaskovich, M.A.T. 2019. Effects of microplate type and broth additives
on microdilution MIC susceptibility assays. Antimicrobial Agents and
Chemotherapy 63(10): e01760-18. https://doi.org/10.1128/AAC.01760-18
Kenshole, E., Herisse, M., Michael, M. &
Pidot, S.J. 2021. Natural product discovery through microbial genome mining. Current
Opinion in Chemical Biology 60: 47-54. https://doi.org/10.1016/j.cbpa.2020.07.010
Komal, A. &
Ye, X. 2022. Epigenetic strategies to discover novel fungal secondary
metabolites. Journal of Biomedical Research & Environmental Sciences 3(3): 246-263. https://doi.org/10.37871/jbres1430
Laforest, L.C., Nguyen, T.M., Matsumoto, G.O.,
Ramachandria, P., Chanderbali, A., Kanumuri, S.R.R., Sharma, A., McCurdy, C.R.,
Dang, T.T. & Nadakuduti, S.S. 2025. A chromosome-level Mitragyna
parvifolia genome unveils spirooxindole alkaloid diversification and
mitraphylline biosynthesis. The Plant Cell 37(9): koaf207. https://doi.org/10.1093/plcell/koaf207
Lima, L.M., Nunes, R.R., Muniz, L.I.T., Silva,
W.L. & Nunez, C.V. 2025. Endophytic fungi as enhancers of secondary
metabolite production in Duroia saccifera cell suspension. ACTA
Paulista de Enfermagem 85: e291007. https://doi.org/10.1590/1519-6984.291007
Maehara, S., Agusta, A., Tokunaga, Y., Shibuya,
H. & Hata, T. 2019. Endophyte composition and Cinchona alkaloid
production abilities of Cinchona ledgeriana cultivated in Japan. Journal
of Natural Medicines 73(2): 431-438. https://doi.org/10.1007/s11418-018-1273-z
Maehara, S., Simanjuntak, P., Kitamura, C.,
Ohashi, K. & Shibuya, H. 2011. Cinchona alkaloids are also produced
by an endophytic filamentous fungus living in Cinchona plant. Chemical
and Pharmaceutical Bulletin 59(8): 1073-1074. https://doi.org/10.1248/cpb.59.1073
Maher, C. & Hassan, K.A. 2023. The
Gram-negative permeability barrier: Tipping the balance of the in and the out. PLOS
Pathogens 19(10): e1011744. https://doi.org/10.1128/mbio.01205-23
Majoumouo, M.S., Tincho, M.B., Toghueo, R.M.K.,
Morris, T., Hiss, D.C., Boyom, F.F. & Mandal, C. 2020. Cytotoxicity
potential of endophytic fungi extracts from Terminalia catappa against
human cervical cancer cells. Evidence-Based Complementary and Alternative
Medicine 2020: 8871152. https://doi.org/10.1155/2020/8871152
Martins, D., Nunez, C.V. & Coordenation, I.
2015. Secondary metabolites from Rubiaceae species. Molecules 20(7):
13422-13495. https://doi.org/10.3390/molecules200713422
Mózsik, L., Iacovelli, R., Bovenberg, R.A.L.
& Driessen, A.J.M. 2022. Transcriptional activation of biosynthetic gene
clusters in filamentous fungi. Frontiers in Bioengineering and Biotechnology 10: 901037. https://doi.org/10.3389/fbioe.2022.901037
Nazir, A., Puthuveettil, A.R., Hussain, F.H.N.,
Hamed, K.E. & Munawar, N. 2024. Endophytic fungi: Nature’s solution for
antimicrobial resistance and sustainable agriculture. Frontiers in
Microbiology 15: 1461504. https://doi.org/10.3389/fmicb.2024.1461504
Nicault, M., Zaiter, A., Dumarcay, S.,
Chaimbault, P., Gelhaye, E., Leblond, P. & Bontemps, C. 2021. Elicitation
of antimicrobial active compounds by Streptomyces-fungus co-cultures. Microorganisms 9(1): 178. https://doi.org/10.3390/microorganisms9010178
Ochoa, G., Armijos, L., Figueroa, J.G.,
Jaramillo-Fierro, X. & Solano-Cueva, N. 2025. Optimization of two methods
for the rapid and effective extraction of quinine from Cinchona officinalis. Plants 14(3): 364. https://doi.org/10.3390/plants14030364
Oktavia, L., Evana, E., Fahardita, R. &
Agusta, A. 2023. Optimization of bis-anthraquinones production from endophytic
fungi Diaporthe sp. GNBP-10. Iraqi Journal of Pharmaceutical Sciences 32(1): 160-166. https://doi.org/10.31351/vol32iss1pp160-166
Oktavia, L., Krishna, V.S., Rekha, E.M.,
Fathoni, A., Sriram, D. & Agusta, A. 2020. Anti-mycobacterial activity of
two natural bisanthraquinones: (+)-1,1′-bislunatin and
(+)-2,2′-epicytoskyrin A. IOP Conference Series: Earth and
Environmental Science 591(1): 012025. https://doi.org/10.1088/1755-1315/591/1/012025
Palmer, J.M. & Keller, N.P. 2010. Secondary
metabolism in fungi: Does chromosomal location matter? Current Opinion in
Microbiology 13(4): 431-436. https://doi.org/10.1016/j.mib.2010.04.008
Pellissier, L., Gaudry, A., Lecoultre, N.,
Rutz, A., Allard, P-M., Marcourt, L. & Queiroz, E.F. 2023. Comparative
metabolomic study of fungal foliar endophytes and their long-lived host Astrocaryum
sciophilum: A model for exploring the chemodiversity of host-microbe
interactions. Frontiers in Plant Science 14: 1278745. https://doi.org/10.3389/fpls.2023.1278745
Petrosillo, N. & Granata, G. 2022. Gram
negatives and antimicrobial resistance: Two faces of the same coin. Journal
of Clinical Medicine 11(19): 5574. https://doi.org/10.3390/jcm11195574
Piątek, M., Sheehan, G. & Kavanagh, K.
2021. Galleria mellonella: The versatile host for drug discovery, in
vivo toxicity testing and characterising host–pathogen interactions. Antibiotics 10(12): 1545. https://doi.org/10.3390/antibiotics10121545
Pillay, L.C., Nekati, L., Makhwitine, P.J.
& Ndlovu, S.I. 2022. Epigenetic activation of silent biosynthetic gene
clusters in endophytic fungi using small molecular modifiers. Frontiers in
Microbiology 13: 815008. https://doi.org/10.3389/fmicb.2022.815008
Prajapati, C., Nand, S., Anurag, R. &
Singh, K. 2025. An update of fungal endophyte diversity and strategies for
augmenting therapeutic potential of their potent metabolites: Recent
advancement. Applied Biochemistry and Biotechnology 197: 2799-2866. https://doi.org/10.1007/s12010-024-05098-9
Prestinaci, F., Pezzotti, P. & Pantosti, A.
2015. Antimicrobial resistance: A global multifaceted phenomenon. Pathogens
and Global Health 109(7): 309-318. https://doi.org/10.1179/2047773215Y.0000000030
Rajendran, S., Robertson, L.P., Kosgahakumbura,
L., Fernando, C., Göransson, U., Wang, H., Hettiarachchi, C. & Gunasekera,
S. 2023. Antibacterial eremophilane sesquiterpenoids from Xylaria feejeensis,
an endophytic fungi of the medicinal plant Geophila repens. Fitoterapia 167: 105496. https://doi.org/10.1016/j.fitote.2023.105496
Riss, T.L., Moravec, R.A., Niles, A.L.,
Duellman, S., Benink, H.A., Worzella, T.J., Minor, L., 2016. Cell viability
assays. In The Assay Guidance Manual, edited by Markossian, S.,
Grossman, A., Baskir, H., Arkin, M., Auld, D., Austin, C., Baell, J.,
Brimacombe, K., Chung, T.D.Y., Coussens, N.P., Dahlin, J.L., Devanarayan, V.,
Foley, T.L., Glicksman, M., Gorshkov, K., Grotegut, S., Hall, M.D., Hoare, S.,
Inglese, J., Iversen, P.W., Lal-Nag, M., Li, Z., Manro, J.R., McGee, J.,
Norvil, A., Pearson, M., Riss, T., Saradjian, P., Sittampalam, G.S., Tarselli,
M.A., Trask Jr., O.J., Weidner, J.R., Wildey, M.J., Wilson, K., Xia, M. &
Xu, X. Rockville: Eli Lilly & Company and the National Center for Advancing
Translational Sciences. https://www.ncbi.nlm.nih.gov/books/NBK144065/
Romano, S., Jackson, S.A., Patry, S. &
Dobson, A.D.W. 2018. Extending the "One Strain Many Compounds"
(OSMAC) principle to marine microorganisms. Marine Drugs 16(7): 244. https://doi.org/10.3390/md16070244
Roy, A., Singh, A.K., Hazra, S., Setyawan,
H.Y., Pandit, S., Aji Muhammad, D.R., Cheng, W.H., Raja, V. & Rajeev, M.
2026. Contribution of endophytes for combating multi-drug- resistant pathogens
- A recent review on novel approches. Phytomedicine Plus 6(3): 100980.https://doi.org/10.1016/j.phyplu.2026.100980
Rutkowska, N., Drożdżyński, P.,
Ryngajłło, M. & Marchut-Mikołajczyk, O. 2023. Plants as the
extended phenotype of endophytes, the actual source of bioactive compounds. International
Journal of Molecular Sciences 24(12): 10096. https://doi.org/10.3390/ijms241210096
Rutledge, P.J. & Challis, G.L. 2015.
Discovery of microbial natural products by activation of silent biosynthetic
gene clusters. Nature Reviews Microbiology 13(6): 373-387. https://doi.org/10.1038/nrmicro3496
Sagita, R., Quax, W.J. & Haslinger, K.
2021. Current state and future directions of genetics and genomics of
endophytic fungi for bioprospecting efforts. Frontiers in Bioengineering and
Biotechnology 9: 649906. https://doi.org/10.3389/fbioe.2021.649906
Santos-Aberturas, J. & Vior, N.M. 2022.
Beyond soil-dwelling actinobacteria: Fantastic antibiotics and where to find
them. FEMS Microbiology Reviews 46(2): fuac007. https://doi.org/10.3390/antibiotics11020195
Shenoy, P.N., Bhaskar, S., Manu, M., Likitha,
M.P., Geetha, N., Shailasree, S. & Kini, K.R. 2024. Genome mining and
AntiSMASH analysis of an Endophytic Talaromyces sp. reveal biosynthetic
pathway gene clusters for novel bioactive compounds. Journal of Applied
Biology and Biotechnology 12(3): 229-235. http://doi.org/10.7324/JABB.2024.154874
Shylaja, G. & Sathiavelu, A. 2019.
Evaluation of bioactive metabolites isolated from endophytic fungus Chaetomium
cupreum of the plant Mussaenda luteola. Indian Journal of
Pharmaceutical Education and Research 53(3): S255-S263. https://doi.org/10.5530/ijper.53.3s.95
Shylaja, G., Sasikumar, K. & Sathiavelu, A.
2018. Antimycobacterial potential of resorcinol type lipid isolated from Chaetomium
cupreum, an endophytic fungus from Mussaenda luteola. Bangladesh
Journal of Pharmacology 13(2): 114-119. https://doi.org/10.3329/bjp.v13i2.34860
Silva, D.P.D., Cardoso, M.S. & Macedo, A.J.
2022. Endophytic fungi as a source of antibacterial compounds - A focus on
Gram-negative bacteria. Antibiotics 11(11): 1509. https://doi.org/10.3390/antibiotics11111509
Silva-Beltrán, N.P., Boon, S.A., Ijaz, M.K.,
McKinney, J. & Gerba, C.P. 2024. Antifungal activity and mechanism of
action of natural product derivates as potential environmental disinfectants. Current
Fungal Infection Reports 18(1): kuad036. https://doi.org/10.1093/jimb/kuad036
Subban, K. & Kempken, F. 2023. Insights
into Taxol® biosynthesis by endophytic fungi. Applied Microbiology and
Biotechnology 107(20): 6151-6162. https://doi.org/10.1007/s00253-023-12713-y
Sun, D., Gao, W., Hu, H. & Zhou, S. 2022.
Why 90% of clinical drug development fails and how to improve it? Acta
Pharmaceutica Sinica B 12(7): 3049-3062. https://doi.org/10.1016/j.apsb.2022.02.002
Tang, M., Wang, Z., Zhu, H., Ma, N.L., Yang,
Z., Tian, Y. & Li, H. 2026. Antimicrobial resistance surveillance in the
natural environment: Standardization of minimum inhibitory concentration
breakpoint. New Contaminants 2: e003. https://doi.org/10.48130/newcontam-0025-0023
Tiwari, P. & Bae, H. 2022. Endophytic
fungi: Key insights, emerging prospects, and challenges in natural product drug
discovery. Microorganisms 10(2): 360. https://doi.org/10.3390/microorganisms10020360
Wang, X., Zhang, X., Liu, L., Xiang, M., Wang,
W., Sun, X., Che, Y., Guo, L., Liu, G., Guo, L., Wang, C., Yin, W-B., Stadler,
M., Zhang, X. & Liu, X. 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: 28. https://doi.org/10.1186/s12864-014-1190-9
World Health Organization (WHO). 2025. Global
Antibiotic Resistance Surveillance Report 2025. Geneva: World Health
Organization.
Wu, C.C.C., Stierle, A.A., Stierle, D.B., Chen,
H., Swyers, M., Decker, T., Borkowski, E., Korajczyk, P., Ye, R. & Mondava,
N. 2023. Activation of cryptic biosynthetic gene clusters by fungal artificial
chromosomes to produce novel secondary metabolites. AIMS Microbiology 9(4): 757-779. https://doi.org/10.3934/microbiol.2023039
Wu, J., Chen, D., Li, Q., Feng, T. & Xu, J.
2024. Metabolomics-guided discovery of new dimeric xanthones from co-cultures
of mangrove endophytic fungi Phomopsis asparagi DHS-48 and Phomopsis sp. DHS-11. Marine Drugs 22(3): 102. https://doi.org/10.3390/md22030102
Wulansari, D., Praptiwi, Julistiono, H.,
Nurkanto, A. & Agusta, A. 2016. Antifungal activity of
(+)-2,2′-epicytoskyrin A and its membrane-disruptive action. Makara
Journal of Science 20(4): 160-166. https://doi.org/10.7454/mss.v20i4.6703
Xu, X., Huang, R. & Yin, W-B. 2021. An
optimized and efficient CRISPR/Cas9 system for the endophytic fungus Pestalotiopsis
fici. Applied and Environmental Microbiology 87(22): e01046-21. https://doi.org/10.3390/jof7100809
Zakariyah, R.F., Ajijolakewu, K.A., Ayodele,
A.J., Folami-A, B.I., Samuel, E.P., Otuoze, S.O., Abdulrauf, L.B. & Ahmed,
R.N. 2024. Progress in endophytic fungi secondary metabolites: Biosynthetic
gene cluster reactivation and advances in metabolomics. Bulletin of the
National Research Centre 48: 44. https://doi.org/10.1186/s42269-024-01199-x
Zheng, J., Wang, H., Wang, X., Zeng, S., Yuan,
S. & Yin, T. 2025. Genome mining and OSMAC strategies unveil diverse
secondary metabolites from the endophytic fungus Diaporthe kyushuensis ZMU-48-1 with antifungal activity. Frontiers in Microbiology 16:
1604639. https://doi.org/10.3389/fmicb.2025.16
*Pengarang untuk surat-menyurat;
email: inherni.martiabna@esaunggul.ac.id
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