en Biotechnology پژوهشي Research <span style="font-size:14px;"><span style="font-family:Times New Roman;"><span new="" roman="" times=""><b><span cambria="">Objective:</span></b> This study used in silico methods to explore the physicochemical properties, pharmacokinetic profiles, and molecular interactions of certain fungal-derived compounds with important enzymes in the ethylene and salicylic acid biosynthesis pathways. These enzymes include ACC Synthase (ACS), ACC Oxidase (ACO), Isochorismate Synthase (ICS), and Phenylalanine Ammonia-Lyase (PAL), all known to be involved in plant defense mechanisms triggered by bioactive secondary metabolites produced by Plant Growth-Promoting Fungi (PGPFs)<span cambria="">.</span></span><br> <span new="" roman="" times=""><b>Methods:</b> Volatile and non-volatile PGPF compounds were obtained from PubChem. SwissADME calculated physicochemical properties, while PlantCyc mapped the ethylene and salicylic acid pathways. Avogadro optimized 3D structures for docking using AutoDock-4.2.6, and PyMOL/AutoDockTools analyzed binding energies and interactions. PDBsum evaluated the effects of the compounds on ISR/SAR-related gene expression and stress responses.</span><br> <span new="" roman="" times=""><b>Results:</b> Physicochemical analysis showed that bioactive compounds from Plant Growth-Promoting Fungi have a variety of molecular properties. &beta;-caryophyllene, farnesol, and lovastatin were found to be highly lipophilic (XLogP > 4), indicating good membrane permeability, while hydrophilic compounds like glutathione displayed increased solubility in water. Pharmacokinetic evaluation supported these findings, with most compounds showing minimal inhibition of cytochrome P450, indicating safety. Molecular docking simulations revealed that verrucarin A had the strongest binding affinity to ACC Oxidase (&minus;7.06 kcal/mol) and Phenylalanine Ammonia-Lyase (&minus;8.52 kcal/mol), while abscisic acid showed strong interactions with ACC Synthase (&minus;6.52 kcal/mol) and Isochorismate Synthase (&minus;8.5 kcal/mol). Pathway simulations identified ACC Synthase, ACC Oxidase, Isochorismate Synthase, and Phenylalanine Ammonia-Lyase as key regulatory points in the biosynthesis of ethylene and salicylic acid.</span><br> <span new="" roman="" times=""><b>Conclusion:</b> These findings show that compounds derived from PGPF can alter plant defense pathways through precise enzyme interactions, establishing a biochemical basis for sustainable agricultural practices.<br> <img alt="" src="./files/site1/images/copuediting.png" style="width: 586px; height: 265px;" ></span><br> &nbsp;</span></span> ACC Synthase,ACC Oxidase,Isochorismate Synthase,Phenylalanine Ammonia-Lyase,Volatile Organic Compounds 0 0 http://pbp.medilam.ac.ir/browse.php?a_code=A-10-247-8&slc_lang=en&sid=1 Yeganeh Shafiei yeganeh.shafiei@yahoo.com 10031947532846006631 10031947532846006631 No Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran Bahman Fazeli-Nasab bfazelinasab@gmail.com 10031947532846006632 10031947532846006632 Yes Department of Agronomy and Plant Breeding, Agriculture Institute, Research Institute of Zabol, Zabol, Iran Ali Salehi Sardoei alisalehisardoei1987@gmail.com 10031947532846006633 10031947532846006633 No Crop and Horticultural Science Research Department, South Kerman Agricultural and Natural Resources Research and Education Center, AREEO, Jiroft, Iran