Natural Mutagenesis-Enabled Global Proteomic Study of Metabolic and Carbon Source Implications in Mutant Thermoacidophillic Archaeon Sulfolobus solfataricus PBL2025.

Natural Mutagenesis-Enabled Global Proteomic Study of Metabolic and Carbon Source Implications in Mutant Thermoacidophillic Archaeon Sulfolobus solfataricus PBL2025.
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突变嗜酸古菌硫磺硫化叶菌 PBL2025 中代谢和碳源影响的自然诱变全球蛋白质组学研究。

DOI:
10.1021/acs.jproteome.6b00920
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发表时间:
2017
影响因子:
4.4
通讯作者:
Qiu W
Qiu W
中科院分区:
生物学2区
文献类型:
--
作者:
Qiu W

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嗜热嗜酸的古细菌sulfolobus solfataricus已被广泛用作古细菌系统生物学研究的模式生物。利用其自发突变体PBL2025进行的研究为研究随后诱变诱导的功能过程转移以及反馈抑制的变化提供了有效的代谢基线。在这里,使用定量蛋白质组学和代谢组学进行了一项非靶向代谢研究,以关联inS的变化。solfataricus菌株P2抗PBL2025和葡萄糖和色氨酸作用。该研究与途径富集分析相结合,通过差异化学计量学鉴定出突出的蛋白质。蛋白质组水平定量显示,在这些条件下,超过20%的重叠蛋白质组是差异表达的。代谢诱导的差异表达沿着中央碳代谢以及其他12个显著调控的途径被观察到。目前的研究结果表明,PBL2025能够通过诱导碳代谢以及其他合成代谢途径(如Val、Leu和isoleu生物合成)进行补偿。研究碳源变化后蛋白质丰度的变化也揭示了两种菌株代谢策略的明显差异,其中P2的碳水化合物和核苷酸代谢明显下调,而PBL2025的能量形成下调和糖酵解上调则是混合反应。迄今为止,本研究利用蛋白质和代谢物水平的互补系统生物学观察,为碳水化合物和氨基酸途径的变化提供了最全面的网络。目前的研究结果为通过自然(自发)代谢重接线的分子加工变化提供了独特的见解,以及对热嗜酸菌对环境碳源变化的代谢弹性的系统生物学理解,可能指导古细菌更有效的定向诱变。
The thermoacidophilic crenarchaeonSulfolobus solfataricushas been widely used as a model organism for archaeal systems biology research. Investigation using its spontaneous mutant PBL2025 provides an effective metabolic baseline to study subsequent mutagenesis-induced functional process shifts as well as changes in feedback inhibitions. Here, an untargeted metabolic investigation using quantitative proteomics and metabolomics was performed to correlate changes inS. solfataricusstrains P2 against PBL2025 and under both glucose and tryptone. The study is combined with pathway enrichment analysis to identify prominent proteins with differential stoichiometry. Proteome level quantification reveals that over 20% of the observed overlapping proteome is differentially expressed under these conditions. Metabolic-induced differential expressions are observed along the central carbon metabolism, along with 12 other significantly regulated pathways. Current findings suggest that PBL2025 is able to compensate through the induction of carbon metabolism, as well as other anabolic pathways such as Val, Leu and iso-Leu biosynthesis. Studying protein abundance changes after changes in carbon sources also reveals distinct differences in metabolic strategies employed by both strains, whereby a clear down-regulation of carbohydrate and nucleotide metabolism is observed for P2, while a mixed response through down-regulation of energy formation and up-regulation of glycolysis is observed for PBL2025. This study contributes, to date, the most comprehensive network of changes in carbohydrate and amino acid pathways using the complementary systems biology observations at the protein and metabolite levels. Current findings provide a unique insight into molecular processing changes through natural (spontaneous) metabolic rewiring, as well as a systems biology understanding of the metabolic elasticity of thermoacidophiles to environmental carbon source change, potentially guiding more efficient directed mutagenesis in archaea.
DOI: 10.1111/j.1432-1033.1991.tb15837.x
发表时间: 1991-03-14
期刊: EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子: --
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CONSALVI, V;CHIARALUCE, R;SCANDURRA, R
通讯作者: SCANDURRA, R
DOI: --
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影响因子: 4.8
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期刊: EXTREMOPHILES
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发表时间: 2012-01-01
期刊: EXTREMOPHILES
影响因子: 2.9
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