Department of Bioengineering, Izmir Institute of Technology, Urla, 35430, İzmir, Türkiye, Turkey.
Department of Biotechnology, Graduate School of Natural and Applied Sciences, Ege University, Bornova, İzmir, Türkiye, Turkey.
Microb Cell Fact. 2023 Apr 6;22(1):66. doi: 10.1186/s12934-023-02069-3.
Cycloartane-type triterpenoids possess important biological activities, including immunostimulant, wound healing, and telomerase activation. Biotransformation is one of the derivatization strategies of natural products to improve their bioactivities. Endophytic fungi have attracted attention in biotransformation studies because of their ability to perform modifications in complex structures with a high degree of stereospecificity.
This study focuses on biotransformation studies on cyclocephagenol (1), a novel cycloartane-type sapogenin from Astragalus species, and its 12-hydroxy derivatives (2 and 3) to obtain new telomerase activators. Since the hTERT protein levels of cyclocephagenol (1) and its 12-hydroxy derivatives (2 and 3) on HEKn cells were found to be notable, biotransformation studies were carried out on cyclocephagenol and its 12-hydroxy derivatives using Camarosporium laburnicola, an endophytic fungus isolated from Astragalus angustifolius. Later, immunoblotting and PCR-based ELISA assay were used to screen starting compounds and biotransformation products for their effects on hTERT protein levels and telomerase activation. All compounds showed improved telomerase activation compared to the control group.
As a result of biotransformation studies, seven new metabolites were obtained and characterized, verifying the potential of C. laburnicola as a biocatalyst. Additionally, the bioactivity results showed that this endophytic biocatalyst is unique in transforming the metabolites of its host to afford potent telomerase activators.
环阿尔廷型三萜类化合物具有重要的生物活性，包括免疫刺激、伤口愈合和端粒酶激活。生物转化是天然产物衍生化策略之一，可提高其生物活性。由于内生真菌能够以高度立体选择性修饰复杂结构，因此它们在生物转化研究中引起了关注。
本研究专注于环阿屯醇（1）的生物转化研究，这是一种来自黄芪属植物的新型环阿尔廷型甾体皂苷元，及其 12-羟基衍生物（2 和 3），以获得新的端粒酶激活剂。由于在 HEKn 细胞中发现环阿屯醇（1）及其 12-羟基衍生物（2 和 3）的 hTERT 蛋白水平显著，因此使用从窄叶黄花棘豆中分离出的内生真菌 Camarosporium laburnicola 对环阿屯醇及其 12-羟基衍生物进行了生物转化研究。之后，使用免疫印迹和基于 PCR 的 ELISA 测定法筛选起始化合物和生物转化产物对 hTERT 蛋白水平和端粒酶激活的影响。与对照组相比，所有化合物均显示出改善的端粒酶激活作用。
通过生物转化研究，获得并鉴定了 7 种新的代谢产物，证实了 C. laburnicola 作为生物催化剂的潜力。此外，生物活性结果表明，这种内生生物催化剂在转化其宿主的代谢物方面具有独特性，可提供有效的端粒酶激活剂。
