稀有真菌萜类-异腈氨基酸杂化天然产物的发现与生物合成。

IF 16.9
Xing-Yue Chen, Qian Yang, Yi Zou
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引用次数: 0

摘要

萜类非蛋白氨基酸杂化天然产物通常具有复杂的化学结构和重要的生物学功能。在此,我们通过两步基因组挖掘策略从镰刀菌中发现了一组保守且广泛分布的倍半萜-异腈异亮氨酸杂交化合物簇。对衣孢镰刀菌isc簇功能的研究揭示了多种不同寻常的酶转化,主要包括1)单模块非核糖体肽合成酶(NRPS) IscF,该酶具有不寻常的c端转移酶结构域,可催化高度氧化的瓜绿烷型5/7双环倍半萜前体4与T结构域结合的l-异腈异亮氨酸11a在C2─OH上的酯化反应,生成萜类-异腈异亮氨酸杂交天然产物9a (chlamonitrile a)和2)细胞色素P450 (CYP450) IscD。出人意料地催化了9a的异腈异亮氨酸部分的Cα-Cβ脱氢,生成最终产物13a/13b(衣腈E/F)。此外,植物毒性评价实验表明9a及其结构类似物是镰刀菌新的植物毒素。我们的工作提供了从真菌中发现萜类-异腈氨基酸杂化化合物的第一个例子,扩展了我们对NRPS结构域和真菌cyp450的新功能的认识,并揭示了这些化合物在镰镰菌中可能的生物学功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Discovery and Biosynthesis of Rare Fungal Terpenoid-Isonitrile Amino Acid Hybrid Natural Products.

Discovery and Biosynthesis of Rare Fungal Terpenoid-Isonitrile Amino Acid Hybrid Natural Products.

Terpenoid nonproteinogenic amino acid hybrid natural products usually have complex chemical structures and important biological functions. Herein, we discovered a group of conserved and widely distributed clusters of sesquiterpenoid-isonitrile isoleucine hybrid compounds from Fusarium through a two-step genome mining strategy. An investigation of the function of the isc cluster from Fusarium chlamydosporum revealed a variety of unusual enzymatic transformations, which importantly include 1) a single-module nonribosomal peptide synthase (NRPS) IscF featuring an unusual C-terminal transferase domain that catalyses the esterification reaction on C2─OH of a highly oxidised guaiane-type 5/7-bicyclic sesquiterpene precursor 4 with T domain-bound l-isonitrile isoleucine 11a to yield terpenoid-isonitrile isoleucine hybrid natural product 9a (chlamonitrile A) and 2) cytochrome P450 (CYP450) IscD, which unexpectedly catalyses the Cα-Cβ dehydrogenation of the isonitrile isoleucine moiety of 9a, resulting in the final products 13a/13b (chlamonitriles E/F). In addition, phytotoxic evaluation experiments revealed that 9a and its structural analogues are new phytotoxins of Fusarium. Our work provides the first example of the discovery of terpenoid-isonitrile amino acid hybrid compounds from fungi, expands our knowledge of the new functions of NRPS domains and fungal CYP450s, and uncovers the possible biological functions of these compounds in Fusarium.

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