Potent telomerase activators from a novel sapogenin via biotransformation utilizing Camarosporium laburnicola, an endophytic fungus

• Published in: Microbial cell factories 2023-04, Vol.22 (1), p.66-66, Article 66
• Main Authors: Küçüksolak, Melis, Yılmaz, Sinem, Ballar-Kırmızıbayrak, Petek, Bedir, Erdal
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Anti-aging; Ascomycota; Ascomycota - metabolism; Astragalus angustifolius; Biological activity; Biotransformation; Camarosporium laburnicola; Carbon; Catalysis; Chemical properties; Endophytes; Endophytic Fungi; Enzyme activation; Enzyme-linked immunosorbent assay; Enzymes; Fungi; Immunoblotting; Immunostimulants; Industrial microorganisms; Metabolites; Methods; Natural products; Physiological aspects; Protein expression; Proteins; Sapogenin; Sapogenins - metabolism; Saponins; Stereospecificity; Telomerase; Telomerase - metabolism; Telomerase activator; Telomerase reverse transcriptase; Triterpenoids; Wound healing
• ISSN: 1475-2859; 1475-2859
• 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.