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Reconstruction and analysis of genome-scale metabolic models of photosynthetic organisms.

机译:光合生物的基因组规模代谢模型的重建和分析。

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摘要

The scope and breadth of genome-scale metabolic reconstructions has continued to expand over the last decade. However, only a limited number of efforts exist on photosynthetic metabolism reconstruction. Cyanobacteria are an important group of photoautotrophic organisms that can synthesize valuable bio-products by harnessing solar energy. They are endowed with high photosynthetic efficiencies and diverse metabolic capabilities that confer the ability to convert solar energy into a variety of biofuels and their precursors. However, less well studied are the similarities and differences in metabolism of different species of cyanobacteria as they pertain to their suitability as microbial production chassis. Here we assemble, update and compare genome-scale models (iCyt773 and iSyn731) for two phylogenetically related cyanobacterial species, namely Cyanothece sp. ATCC 51142 and Synechocystis sp. PCC 6803. Comparisons of model predictions against gene essentiality data reveal a specificity of 0.94 (94/100) and a sensitivity of 1 (19/19) for the Synechocystis iSyn731 model. The diurnal rhythm of Cyanothece 51142 metabolism is modeled by constructing separate (light/dark) biomass equations and introducing regulatory restrictions over light and dark phases. Specific metabolic pathway differences between the two cyanobacteria alluding to different bioproduction potentials are reflected in both models. In addition to these cyanobacterial species we also develop a genome-scale model for a plant with direct applications to food and bioenergy production (i.e., maize). The metabolic model Zea mays i1563 contains 1,563 genes and 1,825 metabolites involved in 1,985 reactions from primary and secondary maize metabolism. For approximately 42% of the reactions direct evidence for the participation of the reaction in maize was found. We describe results from performing flux balance analysis under different physiological conditions, (i.e., photosynthesis, photorespiration and respiration) of a C4 plant and also explore model predictions against experimental observations for two naturally occurring mutants (i.e., bm1 and bm3). Recently, we develop a second-generation genome-scale metabolic model for the maize leaf to capture C4 carbon fixation by modeling the interactions between the bundle sheath and mesophyll cells. Condition-specific biomass descriptions are introduced that account for amino acids, fatty acids, soluble sugars, proteins, chlorophyll, lingo-cellulose, and nucleic acids as experimentally measured biomass constituents. Compartmentalization of the model is based on proteomic/transcriptomic data and literature evidence. With the incorporation of the information from MetaCrop and MaizeCyc databases, this updated model spans 5824 genes, 8484 reactions, and 8918 metabolites, an increase of approximately five times the size of the earlier i RS1563 model. Transcriptomic and proteomic data is also used to introduce regulatory constraints in the model to simulate the limited nitrogen condition and glutamine synthetase gln1-3 and gln1-4 mutants. In silico results have achieved over 62% accuracy in predicting the direction of change in the metabolite pool under each of the mutant conditions compared to the wild-type condition with 82% accuracy determined in the limited nitrogen condition. The developed model corresponds to the largest and more complete to-date effort at cataloguing metabolism for any plant tissue-type.
机译:在过去的十年中,基因组规模的代谢重建的范围和广度不断扩大。但是,在光合代谢重建方面只有有限的努力。蓝细菌是一组重要的光合自养生物,它们可以利用太阳能来合成有价值的生物产品。它们具有高的光合作用效率和多样化的代谢能力,赋予了将太阳能转化为多种生物燃料及其前体的能力。然而,关于它们作为微生物生产底盘的适用性,不同种类的蓝细菌在代谢方面的相似性和差异性研究较少。在这里,我们组装,更新和比较两个系统发育相关蓝细菌物种(即蓝藻菌种)的基因组规模模型(iCyt773和iSyn731)。 ATCC 51142和集胞藻(Synechochocystis sp。) PCC6803。对模型预测与基因必需性数据的比较显示,对集胞藻iSyn731模型的特异性为0.94(94/100),敏感性为1(19/19)。通过构造单独的(亮/暗)生物量方程并引入对光和暗相的调节限制,可以模拟蓝藻51142代谢的昼夜节律。在两个模型中都反映了两个蓝细菌之间特定的代谢途径差异,这暗示了不同的生物生产潜力。除了这些蓝细菌物种外,我们还开发了一种直接用于食品和生物能源生产(即玉米)的植物的基因组规模模型。代谢模型Zea mays i1563包含1,563个基因和1,825个代谢物,涉及一级和二级玉米代谢的1,985个反应。对于大约42%的反应,发现了反应参与玉米的直接证据。我们描述了在C4植物的不同生理条件下(即光合作用,光呼吸和呼吸作用)下进行通量平衡分析的结果,并针对两种自然发生的突变体(即bm1和bm3)的实验观察探索了模型预测。最近,我们通过对束鞘和叶肉细胞之间的相互作用进行建模,为玉米叶片开发了第二代基因组规模的代谢模型,以捕获C4碳固定。引入了条件特定的生物质描述,这些描述考虑了氨基酸,脂肪酸,可溶性糖,蛋白质,叶绿素,舌质纤维素和核酸,这些是实验测量的生物质成分。该模型的区室化基于蛋白质组/转录组数据和文献证据。通过合并来自MetaCrop和MaizeCyc数据库的信息,此更新的模型涵盖了5824个基因,8484个反应和8918个代谢产物,是早期i RS1563模型的大约五倍。转录组学和蛋白质组学数据也用于在模型中引入调控约束条件,以模拟有限的氮条件和谷氨酰胺合成酶gln1-3和gln1-4突变体。与野生型条件相比,在有限的氮条件下确定的82%准确度,与野生型条件相比,计算机模拟结果在预测每种突变条件下代谢物库的变化方向时,已达到62%以上的准确度。所开发的模型对应于对任何植物组织类型的新陈代谢进行分类的最大,更完整的最新成果。

著录项

  • 作者

    Saha, Rajib.;

  • 作者单位

    The Pennsylvania State University.;

  • 授予单位 The Pennsylvania State University.;
  • 学科 Engineering Chemical.
  • 学位 Ph.D.
  • 年度 2014
  • 页码 205 p.
  • 总页数 205
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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