Module evolution and substrate specificity of fungal nonribosomal peptide synthetases involved in siderophore biosynthesis.
Module evolution and substrate specificity of fungal nonribosomal peptide synthetases involved in siderophore biosynthesis.
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DOI：
10.1186/1471-2148-8-328
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发表时间：
2008-12-03
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;Ripoll DR;Turgeon BG
大多数丝状子囊菌产生高亲和力的铁螯合剂，称为铁载体，通过称为非核糖体肽合成酶（NRPS）的多模块腺苷酸化酶非核糖体生物合成。虽然编码大多数NRPS的基因间歇性地分布在真菌界，但编码负责铁色素铁载体生物合成的铁色素合成酶NRPS的基因是保守的，这提供了追踪其进化和其多模块结构域架构起源的机会。此外，由于许多铁色素的化学是已知的，指导NRPS底物选择的生物化学和结构“规则”可以使用蛋白质结构建模和进化方法来解决。对49个完整的真菌基因组序列的搜索显示，除了粟酒裂殖酵母外，没有一个酵母、壶菌或放线菌基因组包含候选的铁色素合成酶。相比之下，所有丝状子囊菌查询包含至少一个，而存在和数量在担子菌变化。当与其他NRPS分析时，编码铁色素合成酶的基因是单系的。系统发育分析提供了支持的祖先复制事件导致两个主要的谱系。他们还支持提出的假设，即铁色素合成酶来自祖先的六节基因，可能是由完整的NRPS模块的串联复制产生的。从这个祖先基因的个别域或完整模块的经常性损失最好地解释了观察到的现存域架构的多样性。确定了参与底物选择和结合底物氨基和羧基末端的腺苷酸化结构域口袋中的关键残基和区域。铁螯合铁色素合成酶似乎仅限于裂殖酵母，丝状子囊菌和担子菌，并分为两个主要谱系。系统发育分析表明，域或模块的丢失导致迭代的生物合成机制的进化，允许在生物合成的铁色素产品的灵活性。早先提出的10个氨基酸的NRPS密码，在我们试图推断底物偏好时失败了。相反，我们的分析指出几个地区的结合口袋重要的基板选择，并建议两个位置的代码参与基板锚定，而不是基板的选择。
Most filamentous ascomycete fungi produce high affinity iron chelators called siderophores, biosynthesized nonribosomally by multimodular adenylating enzymes called nonribosomal peptide synthetases (NRPSs). While genes encoding the majority of NRPSs are intermittently distributed across the fungal kingdom, those encoding ferrichrome synthetase NRPSs, responsible for biosynthesis of ferrichrome siderophores, are conserved, which offers an opportunity to trace their evolution and the genesis of their multimodular domain architecture. Furthermore, since the chemistry of many ferrichromes is known, the biochemical and structural 'rules' guiding NRPS substrate choice can be addressed using protein structural modeling and evolutionary approaches. A search of forty-nine complete fungal genome sequences revealed that, with the exception of Schizosaccharomyces pombe, none of the yeast, chytrid, or zygomycete genomes contained a candidate ferrichrome synthetase. In contrast, all filamentous ascomycetes queried contained at least one, while presence and numbers in basidiomycetes varied. Genes encoding ferrichrome synthetases were monophyletic when analyzed with other NRPSs. Phylogenetic analyses provided support for an ancestral duplication event resulting in two main lineages. They also supported the proposed hypothesis that ferrichrome synthetases derive from an ancestral hexamodular gene, likely created by tandem duplication of complete NRPS modules. Recurrent losses of individual domains or complete modules from this ancestral gene best explain the diversity of extant domain architectures observed. Key residues and regions in the adenylation domain pocket involved in substrate choice and for binding the amino and carboxy termini of the substrate were identified. Iron-chelating ferrichrome synthetases appear restricted to fission yeast, filamentous ascomycetes, and basidiomycetes and fall into two main lineages. Phylogenetic analyses suggest that loss of domains or modules led to evolution of iterative biosynthetic mechanisms that allow flexibility in biosynthesis of the ferrichrome product. The 10 amino acid NRPS code, proposed earlier, failed when we tried to infer substrate preference. Instead, our analyses point to several regions of the binding pocket important in substrate choice and suggest that two positions of the code are involved in substrate anchoring, not substrate choice.
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影响因子：
8
作者：
Kalinina, OV;Mironov, AA;Rakhmaninova, AB
通讯作者：
Rakhmaninova, AB
影响因子：
3.5
作者：
Cramer, Robert A., Jr.;Stajich, Jason E.;Perfect, John R.
通讯作者：
Perfect, John R.
影响因子：
2.9
作者：
Jogl, G;Tong, L
通讯作者：
Tong, L
影响因子：
10.7
作者：
Elemento, O;Gascuel, O;Lefranc, MP
通讯作者：
Lefranc, MP
影响因子：
3.2
作者：
HOROWITZ, NH;CHARLANG, G;WILLIAMS, NP
通讯作者：
WILLIAMS, NP