A Multifunctional Cytochrome P450 and a Meroterpenoid Cyclase in the Biosynthesis of Fungal Meroterpenoid Atlantinone B

A Multifunctional Cytochrome P450 and a Meroterpenoid Cyclase in the Biosynthesis of Fungal Meroterpenoid Atlantinone B
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多功能细胞色素 P450 和类萜环化酶在真菌类萜 Atlantinone B 生物合成中的作用

DOI:
10.1021/acs.orglett.2c00684
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发表时间:
2022-04-08
期刊:
影响因子:
5.2
通讯作者:
Li, Jun
Li, Jun
中科院分区:
化学1区
文献类型:
--
作者:
Qi, Bo-wen;Li, Na;Li, Jun

文献摘要

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在产黄青霉MT-40中发现了Atlantinone B(10)的生物合成基因簇。由该簇编码的多功能细胞色素P450(CYP 3D)负责形成独特的内酯桥环和Atlantinone B的16 β-羟基,并且新的萜烯环化酶(CYP 3C)可以前所未有地接受脱甲基底物环氧法尼基-DMOA(4a)以生成三个双环部分萜类化合物(5a-5c)。该研究为组合合成结构多样的单萜类药物奠定了基础。
The biosynthetic gene cluster of atlantinone B (10) was discovered in Penicillium chrysogenum MT-40. A multifunctional cytochrome P450 (AtlD) encoded by the cluster is responsible for the formation of the unique lactone-bridged ring and the 16 beta-hydroxyl of atlantinone B, and a new terpene cyclase (AtlC) can unprecedentedly accept the demethylated substrate epoxyfarnesyl-DMOA (4a) to generate three bicyclic meroterpenoids (5a-5c). This study paves the way for combinatorial synthesis of structurally diverse meroterpenoids for drug discovery.