Sequence-based analysis of metabolic demands for protein synthesis in prokaryotes

Constraints-based models for microbial metabolism can currently be constructed on a genome-scale. These models do not account for RNA and protein synthesis. A scalable formalism to describe translation and transcription that can be integrated with the existing metabolic models is thus needed. Here, we developed such a formalism. The fundamental protein synthesis network described by this formalism was analysed via extreme pathway and flux balance analyses. The protein synthesis network exhibited one extreme pathway per messenger RNA synthesized and one extreme pathway per protein synthesized. The key parameters in this network included promoter strengths, messenger RNA half-lives, and the availability of nucleotide triphosphates, amino acids, RNA polymerase, and active ribosomes. Given these parameters, we were able to calculate a cell's material and energy expenditures for protein synthesis using a flux balance approach. The framework provided herein can subsequently be integrated with genome-scale metabolic models, providing a sequence-based accounting of the metabolic demands resulting from RNA and protein polymerization.