Reconstruction of the central carbon metabolism of Aspergillus niger.

Helga David, Mats Akesson, Jens Nielsen
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引用次数: 103

Abstract

The topology of central carbon metabolism of Aspergillus niger was identified and the metabolic network reconstructed, by integrating genomic, biochemical and physiological information available for this microorganism and other related fungi. The reconstructed network may serve as a valuable database for annotation of genes identified in future genome sequencing projects on aspergilli. Based on the metabolic reconstruction, a stoichiometric model was set up that includes 284 metabolites and 335 reactions, of which 268 represent biochemical conversions and 67 represent transport processes between the different intracellular compartments and between the cell and the extracellular medium. The stoichiometry of the metabolic reactions was used in combination with biosynthetic requirements for growth and pseudo-steady state mass balances over intracellular metabolites for the quantification of metabolic fluxes using metabolite balancing. This framework was employed to perform an in silico characterisation of the phenotypic behaviour of A. niger grown on different carbon sources. The effects on growth of single reaction deletions were assessed and essential biochemical reactions were identified for different carbon sources. Furthermore, application of the stoichiometric model for assessing the metabolic capabilities of A. niger to produce metabolites was evaluated by using succinate production as a case study.

黑曲霉中心碳代谢的重建。
通过整合黑曲霉及相关真菌的基因组学、生化和生理学信息,确定了黑曲霉中心碳代谢的拓扑结构,重构了黑曲霉的代谢网络。重建的网络可作为未来曲霉基因组测序项目中基因标注的有价值的数据库。在代谢重建的基础上,建立了包含284种代谢物和335种反应的化学计量模型,其中268种代表生化转化,67种代表细胞内不同区室之间以及细胞与细胞外介质之间的转运过程。代谢反应的化学计量学与生长的生物合成需求和细胞内代谢物的准稳态质量平衡相结合,利用代谢物平衡对代谢通量进行量化。该框架被用来对生长在不同碳源上的黑曲霉的表型行为进行计算机表征。评估了单反应缺失对生长的影响,并确定了不同碳源的必要生化反应。此外,以琥珀酸盐的生产为例,评价了化学计量模型在评估黑曲霉代谢能力方面的应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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