A systems level approach to study metabolic networks in prokaryotes with the aromatic amino acid biosynthesis pathway.

Abstract

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.