V K Priya, Sinha Somdatta
National Institute of Technology Calicut, Kattangal, Kerala, India.
Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal, India.
Front Genet. 2023 Jan 16;13:1084727. doi: 10.3389/fgene.2022.1084727. eCollection 2022.
Metabolism of an organism underlies its phenotype, which depends on many factors, such as the genetic makeup, habitat, and stresses to which it is exposed. This is particularly important for the prokaryotes, which undergo significant vertical and horizontal gene transfers. In this study we have used the energy-intensive Aromatic Amino Acid (Tryptophan, Tyrosine and Phenylalanine, TTP) biosynthesis pathway, in a large number of prokaryotes, as a model system to query the different levels of organization of metabolism in the whole intracellular biochemical network, and to understand how perturbations, such as mutations, affects the metabolic flux through the pathway - in isolation and in the context of other pathways connected to it. Using an agglomerative approach involving complex network analysis and Flux Balance Analyses (FBA), of the Tryptophan, Tyrosine and Phenylalanine and other pathways connected to it, we identify several novel results. Using the reaction network analysis and Flux Balance Analyses of the Tryptophan, Tyrosine and Phenylalanine and the genome-scale reconstructed metabolic pathways, many common hubs between the connected networks and the whole genome network are identified. The results show that the connected pathway network can act as a proxy for the whole genome network in Prokaryotes. This systems level analysis also points towards designing functional smaller synthetic pathways based on the reaction network and Flux Balance Analyses analysis.
生物体的新陈代谢是其表型的基础，而表型取决于许多因素，如基因组成、栖息地以及它所面临的压力。这对于原核生物尤为重要，因为它们会经历大量的垂直和水平基因转移。在本研究中，我们将大量原核生物中能量密集型的芳香族氨基酸（色氨酸、酪氨酸和苯丙氨酸，TTP）生物合成途径作为一个模型系统，以探究整个细胞内生化网络中不同层次的代谢组织，并了解诸如突变等扰动如何影响该途径的代谢通量——单独以及在与其相连的其他途径的背景下。通过一种涉及复杂网络分析和通量平衡分析（FBA）的凝聚方法，对色氨酸、酪氨酸、苯丙氨酸及其相连的其他途径进行分析，我们得出了几个新的结果。通过对色氨酸、酪氨酸、苯丙氨酸的反应网络分析以及通量平衡分析和基因组规模重建的代谢途径，我们确定了相连网络与整个基因组网络之间的许多共同枢纽。结果表明，在原核生物中，相连的途径网络可以作为整个基因组网络的替代物。这种系统层面的分析还指出，可基于反应网络和通量平衡分析来设计功能更简单的合成途径。
