Reconstruction of the central carbon metabolism of Aspergillus niger

Reconstruction of the central carbon metabolism of Aspergillus niger
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DOI:
10.1046/j.1432-1033.2003.03798.x
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发表时间:
2003-11-01
期刊:
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子:
--
通讯作者:
Nielsen, J
Nielsen, J
中科院分区:
其他
文献类型:
--
作者:
David, H;Åkesson, M;Nielsen, J

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通过整合尼日尔曲霉及其相关真菌的基因组、生化和生理信息,确定了该菌中心碳代谢的拓扑结构,并重建了其代谢网络。重建的网络可以作为一个有价值的数据库,在未来的曲霉基因组测序计划中确定的基因注释。基于代谢重建,建立了一个化学计量模型,包括284种代谢产物和335个反应,其中268个代表生化转化,67个代表不同细胞内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与生长的生物合成要求和细胞内代谢物的伪稳态质量平衡相结合用于定量。阳离子代谢通量使用代谢平衡。该框架被用于执行A的表型行为的计算机表征。尼日尔生长在不同的碳源。评估了对单反应缺失生长的影响,并确定了不同碳源的基本生化反应。此外,还讨论了化学计量模型在评价A.通过使用琥珀酸生产作为案例研究来评价黑曲霉生产代谢物的尼日尔。
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 quanti. cation 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.