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Fendi Setiawan
Doctoral Program, Lampung University, Bandar Lampung-35145 (Indonesia)
Agriculture, Biological Sciences & Forestry Biochemistry, Genetics & Molecular Biology Chemical Engineering, Chemistry & Bioengineering Chemistry Energy Environmental Science Immunology & microbiology Materials Science & Nanotechnology Mathematics Physics

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Chemical Profile of The Ethyl Acetate Extract of Aspergillus sydowi, 22-PLP1-F1, as Antibacterial Agent Against Clinically Resistant Strains of Staphylococcus aureus and Pseudomonas aeruginosa Andi Setiawan; Fendi Setiawan; Susianti Susianti; Wawan Abdullah Setiawan; Peni Ahmadi; Riski Pangestu; John Hendri; Ni Luh Gede Ratna Juliasih
Journal of Multidisciplinary Applied Natural Science Vol. 5 No. 1 (2025): Journal of Multidisciplinary Applied Natural Science
Publisher : Pandawa Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.47352/jmans.2774-3047.238

Abstract

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.
OSMAC-Activated Alkaloid Diversity in a Mangrove Aspergillus sp. PLP1-F1 Drives Host-Directed Antibacterial Mechanisms Fendi Setiawan; Wawan A Setiawan; Rudy T M Situmeang; Yuli Ambarwati; Ni Luh Gede Ratna Juliasih; Susianti Susianti; Peni Ahmadi; Masayoshi Arai; Andi Setiawan
Journal of Multidisciplinary Applied Natural Science Vol. 6 No. 3 (2026): Journal of Multidisciplinary Applied Natural Science
Publisher : Pandawa Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.47352/jmans.2774-3047.441

Abstract

The growing threat of multidrug-resistant (MDR) pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa necessitates discovery strategies that move beyond conventional single-target antibiotics. Here, we report a dereplication-guided pipeline applied to the mangrove-derived fungus Aspergillus sp. PLP1-F1, cultivated under an one strain–many compounds (OSMAC) solid-state fermentation using agro-industrial waste substrates to activate cryptic biosynthetic pathways. Molecular networking revealed 24 compounds with diverse chemical structures, including spiro-γ-dilactone, chinulin, anthraquinoline, notoamides, epi-fiscalins, okaramines, aspergillides, and cinatrins. The fungal extract exhibited potent antibacterial against resistant pathogen with a minimum inhibition concentration (MIC) of 250 µg/mL. To support these findings, pharmacokinetic profiling (ADME) identified 13 metabolites with favorable drug-likeness properties. Molecular docking against the bacterial division protein FtsZ highlighted three lead candidates epi-fiscalin C (16) (-8.89 kcal/mol), notoamide A (20) (-9.05 kcal/mol), and notoamide O (21) (-8.52 kcal/mol) with superior binding affinities compared to ciprofloxacin (-8.23 kcal/mol), suggesting interference with bacterial cytokinesis. Protein–protein interaction analyses further demonstrated that these alkaloids modulate host signaling networks, including EGFR–MAPK, PI3K–mTOR, caspase-mediated apoptosis, and matrix metalloproteinases. Functional enrichment additionally implicated IL‑17 signaling and neutrophil extracellular trap formation, pathways central to antibacterial immunity and inflammation control. Notably, FtsZ was not a central hub within the interaction networks, indicating that direct bacterial inhibition likely functions as a supportive mechanism alongside host-directed effects. Collectively this study underscores the value of OSMAC-driven metabolomics and systems pharmacology in accelerating natural product discovery, offering a scalable framework for identifying marine fungal metabolites with complex, resistance-resilient mechanisms of action.
Shrimp Shell-Based Solid-State Fermentation Promotes Dual Antibacterial and Cytotoxic Metabolite in Kocuria palustris 19C38A1 Widyastuti Widyastuti; Fendi Setiawan; Ety Apriliana; Wawan A Setiawan; Peni Ahmadi
Journal of Multidisciplinary Applied Natural Science Vol. 6 No. 3 (2026): Journal of Multidisciplinary Applied Natural Science
Publisher : Pandawa Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.47352/jmans.2774-3047.445

Abstract

The growing impact of antimicrobial resistance (AMR) and cancer highlights the need to develop new and more effective therapeutic agents. Here, we explore a solid-state fermentation (SSF) strategy using shrimp-shell waste to stimulate secondary metabolite of marine Kocuria palustris 19C38A1. Bioautography-guided screening revealed that polar components of the extract (C38FA) showed antibacterial activity against multidrug-resistant Staphylococcus aureus (MIC = 250 µg/mL), The same fraction demonstrated pronounced cytotoxicity, inhibiting cell viability of A549 and HeLa cancer cells by 89% and 98%, respectively, at 100 μg mL-1 concentration, while showing weaker activity toward MCF-7 cells. Dereplication analysis using LC–MS/MS has annotated six putative metabolites such as terpendole B (1), p-hydroxyphenyl­acetylglutamic acid (2), istamycin C1 (3), lankacidin C (4), anthelmycin (5), and octacosa-hexaenoic acid (6) with mass accuracies within ±0.3 ppm. Notably, four of these compounds have well established antibacterial or cytotoxic properties, consistent with the dual in vitro bioactivity observed. ADME predictions suggested that compounds 1 and 2 are the most promising drug-like candidates, showing high gastrointestinal absorption and low cytochrome P450 liability. Furthermore, computational target prediction indicated potential interactions with proteases, kinases, oxidoreductases, and EGFR associated pathways, further hinting at their dual activity multifunctionality. Molecular docking suggested that compound 1 binds to FtsZ and EGFR, with predicted binding energies of -6.89 and -9.03 kcal/mol, respectively. Collectively, this work suggests that shrimp-shell waste can serve as a sustainable biogenic elicitor that induces marine actinobacteria to produce metabolites with dual pharmacological activities under SSF. These findings highlight a sustainable method for discovering potential dual activity antibacterial and anticancer bioactive compounds with therapeutic potential.
Co-Authors Andi Setiawan Ety Apriliana John Hendri Masayoshi Arai Ni Luh Gede Ratna Juliasih Peni Ahmadi Peni Ahmadi Peni Ahmadi Riski Pangestu Rudy T M Situmeang Susianti Susianti Susianti Susianti Wawan A Setiawan Wawan Abdullah Setiawan Widyastuti Widyastuti Yuli Ambarwati