Concise Biosynthesis of Phenylfuropyridones in Fungi
Concise Biosynthesis of Phenylfuropyridones in Fungi
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DOI：
10.1002/anie.202008321
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发表时间：
2020-09-17
影响因子：
16.6
通讯作者：
Tang, Yi
中科院分区：
文献类型：
--
作者：
Zhang, Zhuan;Qiao, Tianzhang;Tang, Yi
真菌中的苯基呋喃并吡啶酮类天然产物具有广泛的抗菌活性和细胞毒性，并能增强唑类抗真菌化合物的活性。我们通过异源重组pfp途径阐明了citridone家族化合物的生物合成途径。我们证明，这个家庭的多个成员可以从一个reactiveortho-quinone methide（o-QM）中间体通过电环化，环异构化，或共轭加成。在环氧化物形成P450酶的催化下，柠檬酮B中季碳中心的形成，随后是碳骨架重排。我们的研究结果展示了自然界如何收获ano-QM中间体的反应性，以生物合成复杂的天然产物。
Phenylfuropyridone natural products from fungi exhibit a range of antibacterial and cytotoxicity activities, and can potentiate azole antifungal compounds. We elucidated the biosynthetic pathway of compounds in the citridone family through heterologous reconstitution of thepfppathway. We demonstrate that multiple members of this family can be accessed from a reactiveortho-quinone methide (o-QM) intermediate through electrocyclization, cycloisomerization, or conjugate addition. Formation of the quaternary carbon center in citridone B is catalyzed by an epoxide-forming P450 enzyme, followed by carbon skeletal rearrangement. Our results showcase how nature harvests the reactivities of ano-QM intermediate to biosynthesize complex natural products.