Elucidation of the biosynthetic pathways of timosaponins reveals the antifungal mechanisms in Anemarrhena asphodeloides

作者：Baolian Fan, Zhongju Ji, Min Zhu, Yidu Chen, Jincai Liang, Yu Li, Runduan Yi, Chenxu Liu, Lijun Wang, Ningwei Shi, Tingxing Yang, Ruoshi Huang, Yang Lü, Aijia Ji, Zhongqiu Liu, Lixin Duan · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.01.049 · 被引用次数：5 · 研究领域：Phytochemical Studies and Bioactivities、Marine Sponges and Natural Products、Magnolia and Illicium research

2,3-oxidosqualene cyclase AaOSCR12 is the only identified CAS in Anemarrhena asphodeloides , which directly determines the synthesis and accumulation of subsequent timosaponins. Then the divergence step catalyzed by AaSMT1 and AaSSR2, separately metabolizing into phytosterol and cholesterol pathway. Furthermore, the antifungal efficacy of spirostanol-type timosaponin III is superior to that of furostanol-type timosaponin II, potentially associated with the plant defense mechanisms involving the steroid sapogenin 26-O-β-glucosidase AaF26G1 by unraveled the logic of the conversion from furostanol-type timosaponins to spirostanol-type timosaponins. • Phytosterols and timosaponins biosynthesis pathways were investigated. • SMT1 and SSR2 control the diverging steps of phytosterol and cholesterol biosynthesis. • Conversion mechanisms from furostanol-type timosaponins to spirostanol-type timosaponins are controlled by AaF26G1. • The antifungal efficacy of timosaponin III is superior to that of timosaponin BII. Timosaponins, as steroidal saponins, are the primary active constituents and quality biomarkers in Anemarrhena asphodeloides Bunge. Despite their significance, the biosynthetic pathways of timosaponins have not been thoroughly investigated. This study aims to delineate the biosynthetic pathway of timosaponins in A. asphodeloides , elucidate the catalytic mechanisms of the key cycloartenol synthase (CAS), and investigate the antifungal properties of timosaponins. Genes were clo...