Li Changfu, Li Yuanjun, Wang Jinxu, Lu Fengliu, Zheng Lifen, Yang Lu, Sun Wenwen, Ro Dae-Kyun, Qu Xudong, Wu Yihan, Zhang Yansheng
Shanghai Key Laboratory of Bio-Energy Crops, Synthetic Biology Research Center, School of Life Sciences, Shanghai University, Shanghai, 200444, China.
School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China.
Plant J. 2025 Jan;121(2):e17199. doi: 10.1111/tpj.17199. Epub 2024 Dec 6.
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.
黄原内酯，也被描述为裂环愈创木内酯，是一类具有多种生物活性的独特倍半萜内酯（STLs）。大多数黄原内酯是基于其内酯环位置的12,8-内酯。迄今为止，导致黄原内酯的生物合成途径一直难以捉摸，尤其是自然界如何创造出黄原骨架这一问题由来已久。本研究报道了重要的12,8-黄原内酯8-表黄檀内酯完整生物合成途径的阐明。黄原型骨架直接由中心前体金合欢烯型倍半萜金合欢烯A酸通过一种不寻常的细胞色素P450催化的氧化重排衍生而来。随后，在这个黄原型骨架内形成一个12,8-内酯环，从而产生黄原内酯。黄原内酯的生物合成途径与之前统一的多种12,6-愈创木内酯的生物合成途径形成对比，在后者中，12,6-内酯环的形成先于金合欢烯型骨架向愈创木烷型结构的转化。8-表黄檀内酯完整生物合成途径的发现为利用合成生物学策略在微生物中生产黄原内酯开辟了新的机会。
