An independent biosynthetic route to frame a xanthanolide-type sesquiterpene lactone in Asteraceae

• Published in: The Plant journal : for cell and molecular biology 2024-12
• Main Authors: Li, Changfu, Li, Yuanjun, Wang, Jinxu, Lu, Fengliu, Zheng, Lifen, Yang, Lu, Sun, Wenwen, Ro, Dae-Kyun, Qu, Xudong, Wu, Yihan, Zhang, Yansheng
• Format: Article
• Language: English
• ISSN: 1365-313X; 1365-313X
• DOI: 10.1111/tpj.17199

Xanthanolides, also described as seco-guaianolides, are unique sesquiterpene lactones (STLs) with diverse bioactivities. Most of xanthanolides are 12,8-olides based on the position of their lactone ring. The biosynthetic pathway leading to xanthanolides has hitherto been elusive, especially how nature creates the xanthane skeleton is a long-standing question. This study reports the elucidation of a complete biosynthetic pathway to the important 12,8-xanthanolide 8-epi-xanthatin. The xanthane-type backbone is directly derived from the central precursor germacrene-type sesquiterpene, germacrene A acid, via oxidative rearrangement, catalyzed by an unusual cytochrome P450. Subsequently, a 12,8-lactone ring is formed within this xanthane-type backbone resulting in xanthanolides. The biosynthetic pathway for xanthanolides contrasts with the previously unified biosynthetic route for diverse 12,6-guaianolides, in which a 12,6-lactone ring formation precedes the transformation of a germacrene-type skeleton into a guaiane-type structure. The discovery of the full biosynthetic pathway of 8-epi-xanthantin opens new opportunities for producing xanthanolides in microbial organisms using synthetic biology strategies.