Drivers of metabolic diversification: how dynamic genomic neighbourhoods generate new biosynthetic pathways in the Brassicaceae
Drivers of metabolic diversification: how dynamic genomic neighbourhoods generate new biosynthetic pathways in the Brassicaceae
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DOI：
10.1111/nph.16338
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发表时间：
2019-12-28
期刊：
影响因子：
9.4
通讯作者：
Osbourn, Anne
中科院分区：
文献类型：
--
作者：
Liu, Zhenhua;Duran, Hernando G. Suarez;Osbourn, Anne
植物产生一系列具有重要生态功能的特殊代谢产物。新的生物合成途径的进化机制还没有得到很好的理解。在这里，我们利用现有的基因组序列资源，调查三萜生物合成跨越菊科。氧化角鲨烯环化酶（OSC）催化三萜生物合成的第一个关键步骤。对13个已测序的菊科基因组进行系统分析以鉴定所有OSC基因。研究了总共163个OSC基因周围的基因组邻域（GN），以鉴定在这些区域中显著富集的Pfam结构域。所有与所有的OSC的邻居和ESTA基因组分析的比较被用来调查观察到的众多候选三萜生物合成基因簇（BGC）的序列相似性和进化关系。对三种具有代表性的BGC进行了功能分析，并鉴定了它们的三萜途径产物。我们的研究结果表明，植物基因组是显着的塑料，动态GNs产生新的生物合成途径，在不同的拟南芥科谱系通过洗牌的基因编码的核心调色板的三萜多样化的酶，大概是在响应强大的环境选择压力。这些结果通过酶家族的天然组合阐明了植物特异性代谢多样化的基因组基础，这些酶家族可以使用合成生物学来模拟以设计不同的生物活性分子。
Plants produce an array of specialized metabolites with important ecological functions. The mechanisms underpinning the evolution of new biosynthetic pathways are not well-understood. Here, we exploit available genome sequence resources to investigate triterpene biosynthesis across the Brassicaceae. Oxidosqualene cyclases (OSCs) catalyze the first committed step in triterpene biosynthesis. Systematic analysis of 13 sequenced Brassicaceae genomes was performed to identify all OSC genes. The genome neighbourhoods (GNs) around a total of 163 OSC genes were investigated to identify Pfam domains significantly enriched in these regions. All-vs-all comparisons of OSC neighbourhoods and phylogenomic analysis were used to investigate the sequence similarity and evolutionary relationships of the numerous candidate triterpene biosynthetic gene clusters (BGCs) observed. Functional analysis of three representative BGCs was carried out and their triterpene pathway products were elucidated. Our results indicate that plant genomes are remarkably plastic, and that dynamic GNs generate new biosynthetic pathways in different Brassicaceae lineages by shuffling the genes encoding a core palette of triterpene-diversifying enzymes, presumably in response to strong environmental selection pressure. These results illuminate a genomic basis for diversification of plant-specialized metabolism through natural combinatorics of enzyme families, which can be mimicked using synthetic biology to engineer diverse bioactive molecules.