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Genome-Scale Metabolic Model for the Green Alga Chlorella vulgaris UTEX 395 Accurately Predicts Phenotypes under Autotrophic Heterotrophic and Mixotrophic Growth Conditions

机译:绿藻小球藻UTEX 395的基因组规模代谢模型准确预测自养异养和混养生长条件下的表型

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摘要

The green microalga Chlorella vulgaris has been widely recognized as a promising candidate for biofuel production due to its ability to store high lipid content and its natural metabolic versatility. Compartmentalized genome-scale metabolic models constructed from genome sequences enable quantitative insight into the transport and metabolism of compounds within a target organism. These metabolic models have long been utilized to generate optimized design strategies for an improved production process. Here, we describe the reconstruction, validation, and application of a genome-scale metabolic model for C. vulgaris UTEX 395, iCZ843. The reconstruction represents the most comprehensive model for any eukaryotic photosynthetic organism to date, based on the genome size and number of genes in the reconstruction. The highly curated model accurately predicts phenotypes under photoautotrophic, heterotrophic, and mixotrophic conditions. The model was validated against experimental data and lays the foundation for model-driven strain design and medium alteration to improve yield. Calculated flux distributions under different trophic conditions show that a number of key pathways are affected by nitrogen starvation conditions, including central carbon metabolism and amino acid, nucleotide, and pigment biosynthetic pathways. Furthermore, model prediction of growth rates under various medium compositions and subsequent experimental validation showed an increased growth rate with the addition of tryptophan and methionine.
机译:绿色微藻小球藻由于具有储存高脂质含量的能力和天然代谢的多功能性,已被广泛认为是生物燃料生产的有希望的候选者。由基因组序列构建的区室化的基因组规模代谢模型能够定量洞察目标生物体内化合物的运输和代谢。这些代谢模型长期以来一直被用于生成优化的设计策略,以改善生产过程。在这里,我们描述了C. vulgaris UTEX 395,iCZ843的基因组规模代谢模型的重建,验证和应用。基于基因组大小和重建中基因的数量,重建代表了迄今为止任何真核生物光合生物最全面的模型。高度精选的模型可以准确预测在光合自养,异养和合养条件下的表型。该模型已针对实验数据进行了验证,为模型驱动的应变设计和培养基改良以提高产量奠定了基础。计算得出的在不同营养条​​件下的通量分布表明,许多关键途径受氮饥饿条件的影响,包括中心碳代谢以及氨基酸,核苷酸和色素的生物合成途径。此外,在各种培养基组成下对生长速率的模型预测和随后的实验验证表明,添加色氨酸和蛋氨酸可提高生长速率。

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