Autocatalytic sets in E. coli metabolism

Abstract

Background: A central unsolved problem in early evolution concerns self-organization towards higher complexity in chemical reaction networks. In theory, autocatalytic sets have useful properties to help model such transitions. Autocatalytic sets are chemical reaction systems in which molecules belonging to the set catalyze the synthesis of other members of the set. Given an external supply of starting molecules -the food set -and the conditions that (i) all reactions are catalyzed by at least one molecule, and (ii) each molecule can be constructed from the food set by a sequence of reactions, the system becomes a reflexively autocatalytic food-generated network (RAF set). Autocatalytic networks and RAFs have been studied extensively as mathematical models for understanding the properties and parameters that influence self-organizational tendencies. However, despite their appeal, the relevance of RAFs for real biochemical networks that exist in nature has, so far, remained virtually unexplored. Results: Here we investigate the best-studied metabolic network, that of Escherichia coli, for the existence of RAFs. We find that the largest RAF encompasses almost the entire E. coli cytosolic reaction network. We systematically study its structure by considering the impact of removing catalysts or reactions. We show that, without biological knowledge, finding the minimum food set that maintains a given RAF is NP-complete. We apply a randomized algorithm to find (approximately) smallest subsets of the food set that suffice to sustain the original RAF. Conclusions: The existence of RAF sets within a microbial metabolic network indicates that RAFs capture properties germane to biological organization at the level of single cells. Moreover, the interdependency between the different metabolic modules, especially concerning cofactor biosynthesis, points to the important role of spontaneous (non-enzymatic) reactions in the context of early evolution.

Insuperable problems of the genetic code initially emerging in an RNA world

“…Indeed, cellular biochemistry seems to be rife with networked autocatalytic sets (Sousa et al 2015). The facility with which chains of nucleotides can be copied with tolerable accuracy, along with their offering a range of catalytic (Breaker et al, 2003) and regulatory (Breaker, 2012) possibilities, lends plausibility to RNA as a substrate for RAF set formation in the prebiotic world.…”

Autocatalytic chemical networks preceded proteins and RNA in evolution

“…Modern cellular metabolism is enzyme-based, 67 but >60% of enzyme mechanisms described to date involve one or more cofactors (Ribeiro et 68 al., 2018) and 40% of all proteins crystallized have a bound metal relevant to their function 69 (Guengerich, 2016). RAFs can thus be identified in modern metabolism (Sousa et al, 2015) In search of RAFs, we investigated different levels of ancient metabolism preserved in 77 modern cells. Starting with the biosphere level of the KEGG database, we first removed all 78 eukaryote-specific reactions, and then peeled back one more layer of time by examining 79 anaerobic metabolism.…”

Niche emergence as an autocatalytic process in the evolution of ecosystems

“…They have been shown to exist in computational models of chemical reaction networks, as well as in real chemical and biological reaction networks (Hordijk & Steel, 2017). For example, Sousa et al (2015) showed that the metabolic network of E. coli forms a large autocatalytic (RAF) set, containing 98% of the reactions in that metabolic network. Assuming the same holds for most, if not all species, it seems a valid alternative to represent species by the RAF sets formed by their respective metabolic networks, as opposed to representing them by their genomes.…”