Journal of Multidisciplinary Applied Natural Science
##plugins.themes.gdThemes.journalSlogan##
Scopus CiteScore 2024
4.8
Calculated on 05 May, 2025
SJR 2024
0.31
Powered by scimagojr.com
##plugins.themes.gdThemes.journalSlogan##
4.8
Calculated on 05 May, 2025
0.31
Powered by scimagojr.com
https://doi.org/10.47352/jmans.2774-3047.238
Andi Setiawan
Fendi Setiawan
Susianti Susianti
Wawan Abdullah Setiawan
Peni Ahmadi
Riski Pangestu
John Hendri
Ni Luh Gede Ratna Juliasih
Mangrove endophytic fungi can produce bioactive substances with diverse biological functions. This study aims to evaluate the chemical profile of mangrove fungal endophytic extracts that inhibit clinical pathogenic bacteria resistant to various antibiotics. The fungi were collected from Petengoran mangrove forest, Lampung Province. Fungal isolates were grown on shrimp shell media using solid-state fermentation for 14 days. The fungal biomass was extracted using ethyl acetate, and the active components were evaluated using thin layer chromatography. The extract was partitioned with dichloromethane/water and its bioactivity was tested using TLC-bioautography and agar diffusion methods. The active fraction was identified using LC-MS/MS. The LC-MS/MS data was interpreted with SIRIUS 5.8.6, and the drug-likeness and toxicological characteristics were assessed using ADME/Tox and STopTox machine learning tools. Morphological analysis showed that isolate 22PLP1F1 was an Aspergillus sp., with spherical conidia at the hyphae tips. Through phylogenetic analysis it was confirmed that isolate 22PLP1F1 is Aspergillus sydowii with similarity 98.9%. Initial TLC examination indicated the production of alkaloids, polypeptides, and steroids. Antibacterial assays showed that the polar portion inhibited multi-drug resistance (MDR) Staphylococcus aureus, while the active fraction at 2 mg/mL inhibited MDR Pseudomonas aeruginosa. LC-MS/MS analysis revealed a major chromatogram peak at a retention time of 8.67; m/z 488.2196, suggesting a novel derivative of a compound at a retention time of 7.82; m/z 446.208. ADME/Tox analysis indicated that the compounds do not penetrate the BBB but remain in the GI absorption region. Further research is needed to elucidate the active compounds’ mechanism of action and conduct bioengineering studies.
[1] T. M. Coque, R. Canton, A. E. Perez-Cobas, M. D. Fernandez-de-Bobadilla, and F. Baquero. (2023). "Antimicrobial Resistance in the Global Health Network: Known Unknowns and Challenges for Efficient Responses in the 21st Century". Microorganisms. 11 (4). 10.3390/microorganisms11041050.
DOI: https://doi.org/10.3390/microorganisms11041050[2] D. M. P. De Oliveira, B. M. Forde, T. J. Kidd, P. N. A. Harris, M. A. Schembri, S. A. Beatson, D. L. Paterson, and M. J. Walker. (2020). "Antimicrobial Resistance in ESKAPE Pathogens". Clinical Microbiology Reviews. 33 (3). 10.1128/CMR.00181-19.
DOI: https://doi.org/10.1128/CMR.00181-19[3] M. A. Loyola-Cruz, L. U. Gonzalez-Avila, A. Martinez-Trejo, A. Saldana-Padilla, C. Hernandez-Cortez, J. M. Bello-Lopez, and G. Castro-Escarpulli. (2023). "ESKAPE and Beyond: The Burden of Coinfections in the COVID-19 Pandemic". Pathogens. 12 (5). 10.3390/pathogens12050743.
DOI: https://doi.org/10.3390/pathogens12050743[4] S. P. Gaudencio, E. Bayram, L. Lukic Bilela, M. Cueto, A. R. Diaz-Marrero, B. Z. Haznedaroglu, C. Jimenez, M. Mandalakis, F. Pereira, F. Reyes, and D. Tasdemir. (2023). "Advanced Methods for Natural Products Discovery: Bioactivity Screening, Dereplication, Metabolomics Profiling, Genomic Sequencing, Databases and Informatic Tools, and Structure Elucidation". Marine Drugs. 21 (5). 10.3390/md21050308.
DOI: https://doi.org/10.3390/md21050308[5] P. Gatinho, C. Salvador, S. Gutierrez-Patricio, S. Macedo-Arantes, M. R. Martins, A. M. Silva, A. Z. Miller, and A. T. Caldeira. (2024). "From cultural and natural heritage to reservoir of biomedicine: Prospection of bioactive compounds produced by bacterial isolates from caves". International Biodeterioration & Biodegradation. 190. 10.1016/j.ibiod.2024.105773.
DOI: https://doi.org/10.1016/j.ibiod.2024.105773[6] M. Imchen, J. Moopantakath, A. Sreevalsan, and R. Kumavath. (2024). In: "Applications of Metagenomics". 253-269. 10.1016/b978-0-323-98394-5.00006-7.
DOI: https://doi.org/10.1016/B978-0-323-98394-5.00006-7[7] W. M. M. El-Sayed, M. A. A. Abdrabo, and M. M. Hamed. (2023). In: "Marine Ecosystems: A Unique Source of Valuable Bioactive Compounds, (Marine Ecology: Current and Future Developments". 155-183. 10.2174/9789815051995123030007.
DOI: https://doi.org/10.2174/9789815051995123030007[8] N. Job, M. Sarasan, and R. Philip. (2023). "Mangrove-associated endomycota: diversity and functional significance as a source of novel drug leads". Archives of Microbiology. 205 (11): 349. 10.1007/s00203-023-03679-6.
DOI: https://doi.org/10.1007/s00203-023-03679-6[9] P. Toppo, R. Subba, K. Roy, S. Mukherjee, and P. Mathur. (2022). "Elucidating the Strategies for Isolation of Endophytic Fungi and Their Functional Attributes for the Regulation of Plant Growth and Resilience to Stress". Journal of Plant Growth Regulation. 42 (3): 1342-1363. 10.1007/s00344-022-10638-w.
DOI: https://doi.org/10.1007/s00344-022-10638-w[10] H. Jia, L. Wu, R. Liu, J. Li, L. Liu, C. Chen, J. Li, K. Zhang, J. Liao, and Y. Long. (2024). "Penifuranone A: A Novel Alkaloid from the Mangrove Endophytic Fungus Penicillium crustosum SCNU-F0006". International Journal of Molecular Sciences. 25 (9). 10.3390/ijms25095032.
DOI: https://doi.org/10.3390/ijms25095032[11] F. Qin, Z. S. Song, L. Luo, X. L. Bo, F. R. Wu, M. J. Tan, F. F. Wang, X. S. Huang, and H. S. Wang. (2024). "Diisoprenyl Cyclohexene-Type Meroterpenoids with Cytotoxic Activity from a Mangrove Endophytic Fungus Aspergillus sp. GXNU-Y85". Marine Drugs. 22 (2). 10.3390/md22020058.
DOI: https://doi.org/10.3390/md22020058[12] D. Shintianata, M. P. Patria, A. A. Lubis, and U. Sugiharto. (2024). "Potential Carbon Accumulation Rate in the Sediment Mangroves at Ujung Kulon National Park, Banten, Indonesia". IOP Conference Series: Earth and Environmental Science. 1291 (1). 10.1088/1755-1315/1291/1/012010.
DOI: https://doi.org/10.1088/1755-1315/1291/1/012010[13] A. H. Hashem, M. S. Attia, E. K. Kandil, M. M. Fawzi, A. S. Abdelrahman, M. S. Khader, M. A. Khodaira, A. E. Emam, M. A. Goma, and A. M. Abdelaziz. (2023). "Bioactive compounds and biomedical applications of endophytic fungi: a recent review". Microbial Cell Factories. 22 (1): 107. 10.1186/s12934-023-02118-x.
DOI: https://doi.org/10.1186/s12934-023-02118-x[14] O. A. Al-Bedak, R. M. Sayed, and S. H. A. Hassan. (2019). "A new low-cost method for long-term preservation of filamentous fungi". Biocatalysis and Agricultural Biotechnology. 22. 10.1016/j.bcab.2019.101417.
DOI: https://doi.org/10.1016/j.bcab.2019.101417[15] G. Y. Liu, D. Yu, M. M. Fan, X. Zhang, Z. Y. Jin, C. Tang, and X. F. Liu. (2024). "Antimicrobial resistance crisis: could artificial intelligence be the solution?". Military Medical Research. 11 (1): 7. 10.1186/s40779-024-00510-1.
DOI: https://doi.org/10.1186/s40779-024-00510-1[16] A. Setiawan, R. Lutfiah, N. L. G. R. Juliasih, W. A. Setiawan, J. Hendri, and M. Arai. (2022). "Antibacterial activity of EtOAc extract from marine-derived fungus Aspergillus nomiae A12-RF against clinical pathogen bacteria, Staphylococcus aureus". AACL Bioflux. 15 (3): 1413-1421.
[17] A. Setiawan, W. Widyastuti, A. Irawan, O. S. Wijaya, A. Laila, W. A. Setiawan, N. L. G. R. Juliasih, K. Nonaka, M. Arai, and J. Hendri. (2021). "Solid State Fermentation of Shrimp Shell Waste Using Pseudonocardia carboxydivorans 18A13O1 to Produce Bioactive Metabolites". Fermentation. 7 (4). 10.3390/fermentation7040247.
DOI: https://doi.org/10.3390/fermentation7040247[18] I. Choma and W. Jesionek. (2015). "TLC-Direct Bioautography as a High Throughput Method for Detection of Antimicrobials in Plants". Chromatography. 2 (2): 225-238. 10.3390/chromatography2020225.
DOI: https://doi.org/10.3390/chromatography2020225[19] M. C. Landum, R. Felix Mdo, J. Alho, R. Garcia, M. J. Cabrita, F. Rei, and C. M. Varanda. (2016). "Antagonistic activity of fungi of Olea europaea L. against Colletotrichum acutatum". Microbiology Research. 183 : 100-8. 10.1016/j.micres.2015.12.001.
DOI: https://doi.org/10.1016/j.micres.2015.12.001[20] T. J. White, T. Bruns, S. Lee, and J. Taylor. (1990). In: "PCR Protocols". 315-322. 10.1016/b978-0-12-372180-8.50042-1.
DOI: https://doi.org/10.1016/B978-0-12-372180-8.50042-1[21] M. Ludwig, M. Fleischauer, K. Duhrkop, M. A. Hoffmann, and S. Bocker. (2020). "De Novo Molecular Formula Annotation and Structure Elucidation Using SIRIUS 4". Methods in Molecular Biology. 2104 : 185-207. 10.1007/978-1-0716-0239-3_11.
DOI: https://doi.org/10.1007/978-1-0716-0239-3_11[22] K. Duhrkop, L. F. Nothias, M. Fleischauer, R. Reher, M. Ludwig, M. A. Hoffmann, D. Petras, W. H. Gerwick, J. Rousu, P. C. Dorrestein, and S. Bocker. (2021). "Systematic classification of unknown metabolites using high-resolution fragmentation mass spectra". Nature Biotechnology. 39 (4): 462-471. 10.1038/s41587-020-0740-8.
DOI: https://doi.org/10.1038/s41587-020-0740-8[23] M. A. Hoffmann, L. F. Nothias, M. Ludwig, M. Fleischauer, E. C. Gentry, M. Witting, P. C. Dorrestein, K. Duhrkop, and S. Bocker. (2022). "High-confidence structural annotation of metabolites absent from spectral libraries". Nature Biotechnology. 40 (3): 411-421. 10.1038/s41587-021-01045-9.
DOI: https://doi.org/10.1038/s41587-021-01045-9[24] K. Duhrkop, M. Fleischauer, M. Ludwig, A. A. Aksenov, A. V. Melnik, M. Meusel, P. C. Dorrestein, J. Rousu, and S. Bocker. (2019). "SIRIUS 4: a rapid tool for turning tandem mass spectra into metabolite structure information". Nature Methods. 16 (4): 299-302. 10.1038/s41592-019-0344-8.
DOI: https://doi.org/10.1038/s41592-019-0344-8[25] H. Kim, M. Wang, C. Leber, L.-F. Nothias, R. Reher, K. B. Kang, J. J. J. van der Hooft, P. Dorrestein, W. Gerwick, and G. Cottrell. (2020). 10.26434/chemrxiv.12885494.v1.
DOI: https://doi.org/10.26434/chemrxiv.12885494.v1[26] N. Lohit, A. K. Singh, A. Kumar, H. Singh, J. P. Yadav, K. Singh, and P. Kumar. (2024). "Description and In silico ADME Studies of US-FDA Approved Drugs or Drugs under Clinical Trial which Violate the Lipinski’s Rule of 5". Letters in Drug Design & Discovery. 21 (8): 1334-1358. 10.2174/1570180820666230224112505.
DOI: https://doi.org/10.2174/1570180820666230224112505[27] M. Shafira, E. Rifai, D. Gustiniati, and M. Anwar. (2022). "Focus Group Discussion Tindak Pidana Destructive Fishing dan Dampaknya terhadap Keberlanjutan Pariwisata Bahari Kabupaten Pesawaran". JPKMI (Jurnal Pengabdian Kepada Masyarakat Indonesia). 3 (1): 13-26. 10.36596/jpkmi.v3i1.259.
DOI: https://doi.org/10.36596/jpkmi.v3i1.259[28] S. K. Deshmukh, S. Agrawal, V. Prakash, M. K. Gupta, and M. S. Reddy. (2020). "Anti-infectives from mangrove endophytic fungi". South African Journal of Botany. 134 : 237-263. 10.1016/j.sajb.2020.01.006.
DOI: https://doi.org/10.1016/j.sajb.2020.01.006[29] X. Ma, G. Gozaydin, H. Yang, W. Ning, X. Han, N. Y. Poon, H. Liang, N. Yan, and K. Zhou. (2020). "Upcycling chitin-containing waste into organonitrogen chemicals via an integrated process". The Proceedings of the National Academy of Sciences (PNAS). 117 (14): 7719-7728. 10.1073/pnas.1919862117.
DOI: https://doi.org/10.1073/pnas.1919862117[30] J. Mamangkey, L. W. Mendes, A. Z. Mustopa, and A. Hartanto. (2024). "Endophytic Aspergillii and Penicillii from medicinal plants: a focus on antimicrobial and multidrug resistant pathogens inhibitory activity". BioTechnologia (Pozn). 105 (1): 83-95. 10.5114/bta.2024.135644.
DOI: https://doi.org/10.5114/bta.2024.135644[31] A. Ahmad, S. van Vuuren, and A. Viljoen. (2014). "Unravelling the complex antimicrobial interactions of essential oils--the case of Thymus vulgaris (thyme)". Molecules. 19 (3): 2896-910. 10.3390/molecules19032896.
DOI: https://doi.org/10.3390/molecules19032896[32] K. Tamura, G. Stecher, and S. Kumar. (2021). "MEGA11: Molecular Evolutionary Genetics Analysis Version 11". Molecular Biology and Evolution. 38 (7): 3022-3027. 10.1093/molbev/msab120.
DOI: https://doi.org/10.1093/molbev/msab120[33] S. Kumar, T. Gojobori, and B. Gaut. (2023). "Obituary: Masatoshi Nei (1931–2023)". Molecular Biology and Evolution. 40 (6). 10.1093/molbev/msad149.
DOI: https://doi.org/10.1093/molbev/msad149[34] R. A. Samson, N. Yilmaz, J. Houbraken, H. Spierenburg, K. A. Seifert, S. W. Peterson, J. Varga, and J. C. Frisvad. (2011). "Phylogeny and nomenclature of the genus Talaromyces and taxa accommodated in Penicillium subgenus Biverticillium". Studies in Mycology. 70 (1): 159-83. 10.3114/sim.2011.70.04.
DOI: https://doi.org/10.3114/sim.2011.70.04[35] Q. Meng, X. Guo, J. Wu, D. Liu, Y. Gu, J. Huang, A. Fan, and W. Lin. (2022). "Prenylated notoamide-type alkaloids isolated from the fungus Aspergillus sclerotiorum and their inhibition of NLRP3 inflammasome activation and antibacterial activities". Phytochemistry. 203 : 113424. 10.1016/j.phytochem.2022.113424.
DOI: https://doi.org/10.1016/j.phytochem.2022.113424[36] S. Tsukamoto, H. Kato, M. Samizo, Y. Nojiri, H. Onuki, H. Hirota, and T. Ohta. (2008). "Notoamides F-K, prenylated indole alkaloids isolated from a marine-derived Aspergillus sp". Journal of Natural Products. 71 (12): 2064-7. 10.1021/np800471y.
DOI: https://doi.org/10.1021/np800471y[37] F. M. R. da Silva, G. M. Paggi, F. R. Brust, A. J. Macedo, and D. B. Silva. (2023). "Metabolomic Strategies to Improve Chemical Information from OSMAC Studies of Endophytic Fungi". Metabolites. 13 (2). 10.3390/metabo13020236.
DOI: https://doi.org/10.3390/metabo13020236[38] D. G. Christensen, X. Xie, N. Basisty, J. Byrnes, S. McSweeney, B. Schilling, and A. J. Wolfe. (2019). "Post-translational Protein Acetylation: An Elegant Mechanism for Bacteria to Dynamically Regulate Metabolic Functions". Frontiers in Microbiology. 10 : 1604. 10.3389/fmicb.2019.01604.
DOI: https://doi.org/10.3389/fmicb.2019.01604[39] S. Prasanna and R. J. Doerksen. (2009). "Topological polar surface area: a useful descriptor in 2D-QSAR". Current Medicinal Chemistry. 16 (1): 21-41. 10.2174/092986709787002817.
DOI: https://doi.org/10.2174/092986709787002817[40] F. Zafar, A. Gupta, K. Thangavel, K. Khatana, A. A. Sani, A. Ghosal, P. Tandon, and N. Nishat. (2020). "Physicochemical and Pharmacokinetic Analysis of Anacardic Acid Derivatives". ACS Omega. 5 (11): 6021-6030. 10.1021/acsomega.9b04398.
DOI: https://doi.org/10.1021/acsomega.9b04398[41] E. L. Ayuk, M. O. Uchegbu, P. I. Ebiem-Kenechukwu, and T. O. Oni. (2024). "Preparation, Characterization, In silico and In vitro Antimicrobial Studies of Phenothiazine-3-sulphonamide Derivatives". Bioactivities. 2 (1): 41-56. 10.47352/bioactivities.2963-654X.215.
DOI: https://doi.org/10.47352/bioactivities.2963-654X.215[42] M. Fekadu, D. Zeleke, B. Abdi, A. Guttula, R. Eswaramoorthy, and Y. Melaku. (2022). "Synthesis, in silico molecular docking analysis, pharmacokinetic properties and evaluation of antibacterial and antioxidant activities of fluoroquinolines". BMC Chemistry. 16 (1): 1. 10.1186/s13065-022-00795-0.
DOI: https://doi.org/10.1186/s13065-022-00795-0[43] A. Daina and V. Zoete. (2016). "A BOILED-Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules". ChemMedChem. 11 (11): 1117-21. 10.1002/cmdc.201600182.
DOI: https://doi.org/10.1002/cmdc.201600182[44] J. V. B. Borba, V. M. Alves, R. C. Braga, D. R. Korn, K. Overdahl, A. C. Silva, S. U. S. Hall, E. Overdahl, N. Kleinstreuer, J. Strickland, D. Allen, C. H. Andrade, E. N. Muratov, and A. Tropsha. (2022). "STopTox: An in Silico Alternative to Animal Testing for Acute Systemic and Topical Toxicity". Environmental Health Perspectives. 130 (2): 27012. 10.1289/EHP9341.
DOI: https://doi.org/10.1289/EHP9341