Biosynthetic investigation of phomopsins reveals a widespread pathway for ribosomal natural products in Ascomycetes
Biosynthetic investigation of phomopsins reveals a widespread pathway for ribosomal natural products in Ascomycetes
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拟茎点菌的生物合成研究揭示了子囊菌中核糖体天然产物的广泛途径
DOI：
10.1073/pnas.1522907113
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发表时间：
2016-03-29
影响因子：
11.1
通讯作者：
Zhang, Qi
中科院分区：
文献类型：
--
作者：
Ding, Wei;Liu, Wan-Qiu;Zhang, Qi
意义子囊菌是一个丰富的天然产物的来源，对人类健康具有重要意义，但生产核糖体合成和后修饰肽（RIPPs），一个普遍存在的一类天然产物，很少有报道在这个真菌门。在这里，我们表明，phomopsins，一个家庭的抗有丝分裂真菌毒素，有一个核糖体的起源，并证明了广泛存在的真菌RiPP途径的环肽，我们长期dikaritins。本文所述的框架为挖掘额外的dikaritin成员和研究该真菌天然产物家族的生物活性和生物合成化学提供了基础。核糖体合成和后修饰肽（RIPPs）的生产很少在真菌中报道，即使这个王国的生物体作为天然产物的多产来源有着悠久的历史。在这里，我们报告了一个调查的phomopsins，抗有丝分裂真菌毒素。我们表明，phomopsin是一种真菌的RIPPs，并证明了广泛存在的一个家庭的真菌环状RIPPs，我们术语dikaritins的生物合成途径。我们将PhomM表征为S-腺苷甲硫氨酸依赖性α-N-甲基转移酶，其将根视素A转化为N，N-二甲基化同源物（根视素E），并表明参与dikaritin生物合成的甲基转移酶已经不同地进化，并且可能具有广泛的底物特异性。基因组挖掘研究在不同菌株中鉴定了8种以前未知的dikaritins，突出了真菌中RiPP生物合成的未开发能力，并为研究该真菌天然产物家族的生物活性和未知生物合成转化奠定了基础。
Significance Ascomycetes are a prolific source of natural products that are of great significance for human health, yet production of ribosomally synthesized and posttranslationally modified peptides (RiPPs), a ubiquitous class of natural products, have rarely been reported in this fungal phylum. Here we show that phomopsins, a family of antimitotic mycotoxins, have a ribosomal origin and demonstrate the widespread presence of a fungal RiPP pathway for cyclic peptides that we term dikaritins. The framework described herein provides a foundation for mining for additional dikaritin members and investigating the biological activities and biosynthetic chemistry of this family of fungal natural products. Production of ribosomally synthesized and posttranslationally modified peptides (RiPPs) has rarely been reported in fungi, even though organisms of this kingdom have a long history as a prolific source of natural products. Here we report an investigation of the phomopsins, antimitotic mycotoxins. We show that phomopsin is a fungal RiPP and demonstrate the widespread presence of a pathway for the biosynthesis of a family of fungal cyclic RiPPs, which we term dikaritins. We characterize PhomM as an S-adenosylmethionine–dependent α-N-methyltransferase that converts phomopsin A to an N,N-dimethylated congener (phomopsin E), and show that the methyltransferases involved in dikaritin biosynthesis have evolved differently and likely have broad substrate specificities. Genome mining studies identified eight previously unknown dikaritins in different strains, highlighting the untapped capacity of RiPP biosynthesis in fungi and setting the stage for investigating the biological activities and unknown biosynthetic transformations of this family of fungal natural products.