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Cysteine and iron accelerate the formation of ribose-5-phosphate, providing insights into the evolutionary origins of the metabolic network structure.

Published version
Peer-reviewed

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Authors

Piedrafita, Gabriel  ORCID logo  https://orcid.org/0000-0001-8701-1084
Castro, Cecilia 
Messner, Christoph B 
Szyrwiel, Lukasz 

Abstract

The structure of the metabolic network is highly conserved, but we know little about its evolutionary origins. Key for explaining the early evolution of metabolism is solving a chicken-egg dilemma, which describes that enzymes are made from the very same molecules they produce. The recent discovery of several nonenzymatic reaction sequences that topologically resemble central metabolism has provided experimental support for a "metabolism first" theory, in which at least part of the extant metabolic network emerged on the basis of nonenzymatic reactions. But how could evolution kick-start on the basis of a metal catalyzed reaction sequence, and how could the structure of nonenzymatic reaction sequences be imprinted on the metabolic network to remain conserved for billions of years? We performed an in vitro screening where we add the simplest components of metabolic enzymes, proteinogenic amino acids, to a nonenzymatic, iron-driven reaction network that resembles glycolysis and the pentose phosphate pathway (PPP). We observe that the presence of the amino acids enhanced several of the nonenzymatic reactions. Particular attention was triggered by a reaction that resembles a rate-limiting step in the oxidative PPP. A prebiotically available, proteinogenic amino acid cysteine accelerated the formation of RNA nucleoside precursor ribose-5-phosphate from 6-phosphogluconate. We report that iron and cysteine interact and have additive effects on the reaction rate so that ribose-5-phosphate forms at high specificity under mild, metabolism typical temperature and environmental conditions. We speculate that accelerating effects of amino acids on rate-limiting nonenzymatic reactions could have facilitated a stepwise enzymatization of nonenzymatic reaction sequences, imprinting their structure on the evolving metabolic network.

Description

Keywords

Amino Acids, Catalysis, Cysteine, Evolution, Molecular, Glucose, Glycolysis, Iron, Magnetic Resonance Spectroscopy, Metabolic Networks and Pathways, Origin of Life, Pentose Phosphate Pathway, Ribosemonophosphates

Journal Title

PLoS Biol

Conference Name

Journal ISSN

1544-9173
1545-7885

Volume Title

19

Publisher

Public Library of Science (PLoS)
Sponsorship
Cancer Research UK (FC001134)
UK Medical Research Council (FC001134)
Wellcome Trust (FC001134)
Wellcome Trust (200829/Z/16/Z)
Bundesministerium für Bildung und Forschung (031L0220A)
UK Medical Research Council (MR/P011705/1)
UK Medical Research Council (MC_UP_A090_1006)
Comunidad de Madrid (Talento program fellowship)