Analysis Of Amino Acid Metabolic Flux For Bacterial Protein Composition

Amino acid compositions are diverse in different sorts of proteins in a living organism. Because biosynthesis pathway is one source of amino acids and the metabolic network has specific topology and reaction constraints, it is unlikely to synthesize amino acids in arbitrary proportion with the same efficiency. Therefore, it is necessary to study the protein residue composition from the aspect of metabolic networks. The availability of more and more genome-scale metabolic networks provides us with the possibility to study the relationship between metabolic network and protein residue composition. Because amino acid metabolism and protein translation are connected by the reactions of aminoacyl-tRNA (aa-tRNA) synthesis, we can study how well amino acid metabolism supports the residue composition in different protein classes.In this work, we used the reconstructed metabolic networks and the constraint-based flux balance analysis, with a novel objective function, namely, maximizing the correlation between the aa-tRNA synthesis fluxes and protein residue compositions, to answer the question of how well the amino acid metabolic network supports the protein residue composition. Our results showed that amino acid metabolic network provides better support for lowly expressed and less conserved proteins.In translation, highly expressed proteins have better optimization for their codon usage, our finding that lowly expressed proteins get better support from the amino acid metabolism indicates that there may exist multi-level optimization in the protein translation process. Though the optimization in codon usage is the major layer affecting protein expression, there is also a certain optimization room in the amino acid metabolic network layer, leading to a better fitness between the amino acid supply and the residue composition in lowly expressed proteins; that is to say, the insufficiency of optimization in the codon usage was compensated in a certain degree by the optimization in the amino acid metabolism in protein translation; based on this finding, we proposed the concept of translation optimization space to systematically understand the optimization strategies in protein translation. At the same time, our results also suggest to some extent the impact of the amino acid metabolic network on the emergence of new genes.