Bioprospecting potential, metabolic profiling, and molecular docking studies of metabolites from endophytic fungi associated with <i>Teucrium stocksianum</i>

Endophytic fungi associated with <i>Tecurium stocksianum</i> signify under-explored repository of promising biologically active metabolites. The aim of this current research was to identify endophytic fungi with antimicrobial properties that are linked to <i>T. stocksianum</i>. Natural compounds found in plants have demonstrated significant potential, but often, the levels of these bioactive substances in plant tissues are insufficient. To tackle this challenge, the study sought to uncover and utilize endophytes. Following cultivation, crude ethyl acetate extracts of the endophytes were screened for antimicrobial, antioxidant, cytotoxic activities and subjected to high resolution LCMS characterization. Among nine of the isolated endophytic fungi, two isolates HS11 and HS12 expressed significant biological activities. Metabolic profiling of the partially purified ethyl acetate extract of the isolate HS12 <i>Fusarium oxysporium</i> led to the detection of potent bioactive molecules, i.e. (5ξ)-11,12-Dihydroxyabieta-8(14),9(11),12-trien-20-oic acid, 2,2′-Methylenebis(4-methyl-6-tert-butyl phenol, L-Phenylalanine and 7-Methoxycoumarin-4-acetic acid. These metabolites have been investigated <i>via</i> molecular docking strategy against a conserved antibiotic resistance protein target of ESKAPE pathogens. Molecular dynamics simulation has further validated these complexes and has been inferred that 2 complex systems are more stable than the (5ξ)-11,12-Dihydroxyabieta-8(14),9(11),12-trien-20-oic acid complex system in a 100 ns time scale. Results inferred high binding affinities of the compounds against the target molecule. Thus, our study demonstrates promising bio-prospecting potential of endophytic fungi associated with <i>T. stocksianum</i> and advocates up-scaling for compound isolation studies; in particular; from candidate HS12 <i>F. oxysporium.</i>与斯图克氏泰库瑞木（Tecurium stocksianum）共生的内生真菌（endophytic fungi），是一类尚未被充分发掘的、蕴含极具应用潜力生物活性代谢产物的资源库。本研究旨在筛选与T. stocksianum共生的具有抗菌活性的内生真菌。植物来源的天然化合物已展现出可观应用潜力，但植物组织内此类生物活性物质的含量往往不足。为应对这一难题，本研究尝试发掘并利用内生真菌。菌株培养完成后，研究人员对内生真菌的粗乙酸乙酯提取物开展了抗菌、抗氧化、细胞毒性活性筛选，并通过高分辨液相色谱-质谱（high resolution LCMS）技术对其进行表征。在所分离得到的9株内生真菌中，HS11与HS12两株菌株展现出了显著的生物活性。对HS12菌株——尖孢镰刀菌（Fusarium oxysporium）——的半纯化乙酸乙酯提取物进行代谢组分析后，研究人员检测到多种强效生物活性分子，分别为：(5ξ)-11,12-二羟基松香-8(14),9(11),12-三烯-20-羧酸、2,2'-亚甲基双(4-甲基-6-叔丁基苯酚)、L-苯丙氨酸以及7-甲氧基香豆素-4-乙酸。研究人员通过分子对接（molecular docking）策略，将上述代谢产物与ESKAPE病原菌的保守抗生素耐药蛋白靶点进行了对接模拟。分子动力学模拟（molecular dynamics simulation）进一步验证了这些复合物的结合情况，结果显示，在100纳秒（ns）的模拟时长内，有两组复合物体系的稳定性优于(5ξ)-11,12-二羟基松香-8(14),9(11),12-三烯-20-羧酸复合物体系。实验结果表明，受试化合物与靶点蛋白均表现出较高的结合亲和力。综上，本研究证实了与T. stocksianum共生的内生真菌具备可观的生物勘探潜力，并建议针对候选菌株HS12（F. oxysporium，尖孢镰刀菌）开展规模化的化合物分离研究。

搜集汇总

背景与挑战

背景概述

该数据集聚焦于与Teucrium stocksianum相关的内生真菌的生物勘探潜力，重点研究了其代谢物的抗菌、抗氧化和细胞毒性活性。通过高分辨率LCMS表征和分子对接模拟，研究从9种分离真菌中识别出两种活性显著的菌株（HS11和HS12），并检测到多种生物活性分子，其中HS12 Fusarium oxysporium的代谢物在对抗ESKAPE病原体耐药蛋白方面显示出高结合亲和力。数据集涵盖了从真菌分离到化合物验证的完整实验过程，突出了内生真菌作为未开发生物活性资源的价值。