Phylogenomics reveals subfamilies of fungal nonribosomal peptide synthetases and their evolutionary relationships.
Phylogenomics reveals subfamilies of fungal nonribosomal peptide synthetases and their evolutionary relationships.
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DOI：
10.1186/1471-2148-10-26
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发表时间：
2010-01-26
影响因子：
3.4
通讯作者：
Turgeon BG
中科院分区：
文献类型：
--
作者：
Bushley KE;Turgeon BG
非核糖体肽合成酶(NRPS)是一种在真菌和细菌中发现的多模块酶，它在没有核糖体的帮助下生物合成肽。虽然它们的代谢产物因其作为药物的救命作用和作为真菌毒素和毒力因子的伤害作用而受到广泛的研究，但对相应的NRPS的系统发育关系以及它们是否可以归入共同功能亚群的了解还很少。我们在38个真菌基因组中鉴定了编码NRPS和NRPS类蛋白的基因，并进行了系统发育分析，以确定真菌NRPS亚家族，评估分类分布，评估亚家族之间的保守水平，并探讨多模块NRPS的进化机制。我们还研究了真菌NRPS(细菌NRPS的代表性样本)与相关腺化酶的关系，包括参与真菌赖氨酸生物合成的α-氨基己酸还原酶(AAR)。系统发育分析确定了真菌NRPS的9个主要亚家族，主要分为两大类：一类是NPS基因，主要编码与细菌NRPS同源的单/双模块酶；另一类是NPS基因，编码的基因主要是多模块的，只有真菌的NRPS。AARs与NRPS的亲缘关系比与其他酰基腺苷化酶的亲缘关系更近。系统发育分析和分类分布表明，在真菌进化之前或早期出现了几个单/双模块亚家族，而两个多模块类群似乎局限于真菌并在真菌中扩展。较老的单/双模块亚家族显示出保守的结构域结构，暗示着功能保守，而多模块NRPS，特别是那些真正的子囊菌所特有的NRPS，显示了不同的结构和产生这种多样性的遗传机制。这项工作是首次描述真菌NRPS亚家族的特征。我们的分析表明，与大多数多模块NRPS相比，单/双模块NRPS具有更古老的起源和更保守的域结构。这也证明了参与真菌赖氨酸生物合成的α-氨基己二酸还原酶与单/双模块NRPS密切相关。几组单/双模块NRPS代谢物被预测在细胞代谢中发挥比多模块NRPS产品更关键的作用。相比之下，NRPS的多模块亚家族起源较晚，仅限于真菌，显示出不太稳定的结构域结构，并且生物合成的代谢物比单/双模块NRPS产品具有更多的生态位特异性功能。特别是，仅限真真菌的NRPS亚家族显示了结构域的广泛获得和丢失的证据，这表明结构域复制和丢失在响应特定生态位压力方面的贡献。
Nonribosomal peptide synthetases (NRPSs) are multimodular enzymes, found in fungi and bacteria, which biosynthesize peptides without the aid of ribosomes. Although their metabolite products have been the subject of intense investigation due to their life-saving roles as medicinals and injurious roles as mycotoxins and virulence factors, little is known of the phylogenetic relationships of the corresponding NRPSs or whether they can be ranked into subgroups of common function. We identified genes (NPS) encoding NRPS and NRPS-like proteins in 38 fungal genomes and undertook phylogenomic analyses in order to identify fungal NRPS subfamilies, assess taxonomic distribution, evaluate levels of conservation across subfamilies, and address mechanisms of evolution of multimodular NRPSs. We also characterized relationships of fungal NRPSs, a representative sampling of bacterial NRPSs, and related adenylating enzymes, including α-aminoadipate reductases (AARs) involved in lysine biosynthesis in fungi. Phylogenomic analysis identified nine major subfamilies of fungal NRPSs which fell into two main groups: one corresponds to NPS genes encoding primarily mono/bi-modular enzymes which grouped with bacterial NRPSs and the other includes genes encoding primarily multimodular and exclusively fungal NRPSs. AARs shared a closer phylogenetic relationship to NRPSs than to other acyl-adenylating enzymes. Phylogenetic analyses and taxonomic distribution suggest that several mono/bi-modular subfamilies arose either prior to, or early in, the evolution of fungi, while two multimodular groups appear restricted to and expanded in fungi. The older mono/bi-modular subfamilies show conserved domain architectures suggestive of functional conservation, while multimodular NRPSs, particularly those unique to euascomycetes, show a diversity of architectures and of genetic mechanisms generating this diversity. This work is the first to characterize subfamilies of fungal NRPSs. Our analyses suggest that mono/bi-modular NRPSs have more ancient origins and more conserved domain architectures than most multimodular NRPSs. It also demonstrates that the α-aminoadipate reductases involved in lysine biosynthesis in fungi are closely related to mono/bi-modular NRPSs. Several groups of mono/bi-modular NRPS metabolites are predicted to play more pivotal roles in cellular metabolism than products of multimodular NRPSs. In contrast, multimodular subfamilies of NRPSs are of more recent origin, are restricted to fungi, show less stable domain architectures, and biosynthesize metabolites which perform more niche-specific functions than mono/bi-modular NRPS products. The euascomycete-only NRPS subfamily, in particular, shows evidence for extensive gain and loss of domains suggestive of the contribution of domain duplication and loss in responding to niche-specific pressures.
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影响因子：
3.5
作者：
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通讯作者：
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通讯作者：
Turgeon BG
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