Maumela Pfariso, Serepa-Dlamini Mahloro Hope
Department of Biotechnology and Food Technology, Faculty of Science, University of Johannesburg, Doornfontein Campus, P.O. Box 17011, Johannesburg 2028, South Africa.
Metabolites. 2024 Mar 13;14(3):163. doi: 10.3390/metabo14030163.
Resistance to anticancer therapeutics is a major global concern. Thus, new anticancer agents should be aimed against novel protein targets to effectively mitigate the increased resistance. This study evaluated the potential of secondary metabolites from a bacterial endophyte, as new anticancer agents, against a novel protein target, fibroblast growth factor. In silico genomic characterization of the sp. strain MHSD_37 was used to identify potential genes involved in encoding secondary metabolites with biological activity. The strain was also exposed to stress and liquid chromatography-mass spectrometry used for the identification and annotation of secondary metabolites of oligopeptide class with anticancer activity. Selected metabolites were evaluated for their anticancer activity through molecular docking and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties analysis. Phylogenetic analysis revealed that strain MHSD_37 shared close evolutionary relationships with at the species level, with no identified relationships at the sub-species level. Both in silico genomic characterization and spectrometry analysis identified secondary metabolites with potential anticancer activity. Molecular docking analysis illustrated that the metabolites formed complexes with the target protein, fibroblast growth factor, which were stabilized by hydrogen bonds. Moreover, the ADMET analysis showed that the metabolites passed the toxicity test for use as a potential drug. Thereby, sp. strain MHSD_37 is a potential novel strain with oligopeptide metabolites that can be used as new anticancer agents against novel protein targets.
对抗癌疗法的耐药性是全球主要关注的问题。因此，新型抗癌药物应针对新的蛋白质靶点，以有效缓解日益增加的耐药性。本研究评估了一种细菌内生菌的次生代谢产物作为新型抗癌药物针对新蛋白质靶点成纤维细胞生长因子的潜力。利用该菌株的计算机基因组特征来鉴定参与编码具有生物活性的次生代谢产物的潜在基因。该菌株还受到应激处理，并采用液相色谱 - 质谱法对具有抗癌活性的寡肽类次生代谢产物进行鉴定和注释。通过分子对接以及吸收、分布、代谢、排泄和毒性（ADMET）特性分析对选定的代谢产物进行抗癌活性评估。系统发育分析表明，菌株MHSD_37在物种水平上与[未提及的物种]具有密切的进化关系，在亚种水平上未发现相关关系。计算机基因组特征分析和光谱分析均鉴定出具有潜在抗癌活性的次生代谢产物。分子对接分析表明，这些代谢产物与靶蛋白成纤维细胞生长因子形成复合物，并通过氢键得以稳定。此外，ADMET分析表明这些代谢产物通过了作为潜在药物的毒性测试。因此，菌株MHSD_37是一种潜在的新型菌株，其寡肽代谢产物可作为针对新蛋白质靶点的新型抗癌药物。
