The modular biochemical reaction network structure of cellular translation

Abstract

Translation is a foundational attribute of all living cells. At the heart of cellular operation, it is a chemical information decoding process that begins with an input string of nucleotides and ends with the synthesis of a specific output string of peptides. The translation process is interconnected with gene expression, physiological regulation, transcription, and responses to signaling molecules, among other cellular functions. However, the underlying biochemical connections between translation, metabolism and polymer biosynthesis that enable translation to occur have not been comprehensively mapped. Here we present a multilayer graph of biochemical reactions describing the translation, polymer biosynthesis and metabolism networks of an Escherichia coli cell. Contrary to our predictions of a continuous mass distribution, the compounds that compose these three layers are distinctly aggregated into three modes regardless of their layer categorization. Multimodal mass distributions are well-known in ecosystems, but this is the first such distribution reported at the biochemical level. The connectivity distributions of the translation and metabolic networks are each likely to be heavy-tailed, but the polymer biosynthesis network is not. A multimodal mass-connectivity distribution indicates that the translation and metabolism networks are each distinct, adaptive biochemical modules, and that the gaps between the modes reflect evolved responses to the functional use of metabolite, polypeptide and polynucleotide compounds. The chemical reaction network of cellular translation opens new avenues for exploring complex adaptive phenomena such as percolation and phase changes in biochemical contexts.

Assessment of Stoichiometric Autocatalysis across Element Groups

“…For example, CO 2 , ATP, NADPH, and H 2 O are kinetically separated during the Calvin cycle because they do not directly react to produce monosaccharides, and activating the Calvin cycle requires monosaccharide phosphates as autocatalysts. Intracellular compartments (e.g., the nucleus or the mitochondria in eukaryotes) or macromolecular centralization of multifaceted processes (e.g., ribosomal subunit interactions) can provide a microscopic structural basis for spatial separation. , Temporal separation can be mediated by vegetative growth and reproductive growth. One underexplored implication for prebiotic chemistry is that a stoichiometric capability for abiotic autocatalysis may be relatively common across elements, but circumstances facilitating effective separation of key food species and reactions may be a more substantial bottleneck to actualizing autocatalytic dynamics under most cosmochemical and geochemical conditions.…”

Origin and Evolution of Translation: A Unifying Perspective Across Time

“…The ribosome is obviously a hub at the level of cellular physiology, as all other translated proteins in a cell must originate there. Yet, many of the macromolecules interact with the broader translation machinery in direct and essential ways [86]. A comprehensive network depicting the proteins and RNAs that perform translation can simultaneously map protein-protein or protein-RNA interactions without omitting or oversimplifying interactions occurring at different scales (Figure 4).…”

“…in a cell [87,88]. Finally, (iii) Cellular: translation is a process of coordinating the activity of dozens of enzyme-and ribozyme-interaction partners and energy transducer molecules to power the process of peptide polymerization against ambient conditions generally favorable for polymer hydrolysis [86,89,90].…”

An assessment of stoichiometric autocatalysis across element groups

“…For example, CO2 and H2O are kinetically separated during photosynthesis; otherwise, CO2 and H2O will spontaneously react to produce monosaccharides under sunlight. Intracellular compartments (e.g., the nucleus or the mitochondria in eukaryotes) or macromolecular centralization of multifaceted processes (e.g., ribosomal subunit interactions) can provide a microscopic structural basis of spatial separation (Cuevas-Zuvirí a et al, 2023;Hartwell et al, 1999). Temporal separation can be mediated by vegetative growth and reproductive growth.…”