Small-molecular metabolic autocatalytic regulators, which are crucial to metabolic pathways, are identified in a novel systems-wide study in different organisms, revealing that in the enzymatic reactions of conserved autocatalytic cycles, the autocatalytic behavior of replicators varies

Kun, Ádám

Papp, Balázs

Szathmáry, Eörs

English

PubMed

Ádám Kun

Balázs Papp

Eörs Szathmáry

Crossref

Computational identification of obligatorily autocatalytic replicators embedded in metabolic networks

Papp, B

Szathmáry, E

ELTE Digital Institutional Repository (EDIT)

Springer - Publisher Connector

Background



If chemical A is necessary for the synthesis of more chemical A, then A has the power of replication (such systems are known as autocatalytic systems). We provide the first systems-level analysis searching for small-molecular autocatalytic components in the metabolisms of diverse organisms, including an inferred minimal metabolism.



Results



We find that intermediary metabolism is invariably autocatalytic for ATP. Furthermore, we provide evidence for the existence of additional, organism-specific autocatalytic metabolites in the forms of coenzymes (NAD+, coenzyme A, tetrahydrofolate, quinones) and sugars. Although the enzymatic reactions of a number of autocatalytic cycles are present in most of the studied organisms, they display obligatorily autocatalytic behavior in a few networks only, hence demonstrating the need for a systems-level approach to identify metabolic replicators embedded in large networks.



Conclusion



Metabolic replicators are apparently common and potentially both universal and ancestral: without their presence, kick-starting metabolic networks is impossible, even if all enzymes and genes are present in the same cell. Identification of metabolic replicators is also important for attempts to create synthetic cells, as some of these autocatalytic molecules will presumably be needed to be added to the system as, by definition, the system cannot synthesize them without their initial presence

Repository of the Academy's Library

3rd: Coenzymes as fossils of an earlier metabolic state.

A Theory of Biochemical Supersystems Baltimore:

A: Determination of the core of a minimal bacterial gene set. Microbiol Mol Biol Rev

A: Modern metabolism as a palimpsest of the RNA world.

A: Structural analyses of a hypothetical minimal metabolism.

Adenine and adenosine salvage pathways in erythrocytes and the role of S-adenosylhomocysteine hydrolase. A theoretical study using elementary flux modes.

Al-Hossainy E, Silverman JA: Adenine nucleotide and lysine transport in Chlamydia psittaci.

AM: Structural and catalytic properties of CMP kinase from Bacillus subtilis: a comparative analysis with the homologous enzyme from Escherichia coli. Arch Biochem Biophys

An expanded genomescale model of Escherichia coli

Before enzymes and templates: theory of surface metabolism. Microbiol Rev

Biochemical diversity for biosynthesis of aromatic amino acids among the cyanobacteria.

Characterization of protein kinase CK2 from Trypanosoma brucei. Mol Biochem Parasitol

Chauvat F: Genetic analysis of amino acid transport in the facultatively heterotrophic cyanobacterium Synechocystis sp. strain 6803.

Chemoton Theory

Compartmental and regulatory mechanisms in the arginine pathways of Neurospora crassa and Saccharomyces cerevisiae. Microbiol Rev

Dorrenstein P: The biosynthesis of nicotinamide adenine dinucleotides in basteria. Vitam Horm

Epigenetic Inheritance and Evolution Oxford:

Evolution of the coenzymes. Biosystems

Expanding metabolic networks: scopes of compounds, robustness, and evolution.

Flux analysis of underdetermined metabolic networks: the quest for the missing constraints. Trends Biotechnol

Formation synthetique d'une substance sucree.

GD: The origin of intermediary metabolism.

Genome-scale analysis of Streptomyces coelicolor A3(2) metabolism. Genome Res

Glycerate kinase of the hyperthermophilic archaeon Thermoproteus tenax: new insights into the phylogenetic distribution and physiological role of members of the three different glycerate kinase classes. BMC Genomics

Goldovsky L: A minimal estimate for the gene content of the last universal common ancestor - exobiology from a terrestrial perspective. Res Microbiol

Highly divergent methyltransferases catalyze a conserved reaction in tocopherol and plastoquinone synthesis in cyanobacteria and photosynthetic eukaryotes. Plant Cell

Ideker T: Modeling methanogenesis with a genome-scale metabolic reconstruction of Methanosarcina barkeri. Mol Syst Biol

KEGG for linking genomes to life and the environment. Nucleic Acids Res 2008, 36(Database issue):D480-D484.

LM: Metabolic functions of duplicate genes in Saccharomyces cerevisiae. Genome Res

Lovley DR: Characterization of metabolism in the Fe(III)-reducing organism Geobacter sulfurreducens by constraint-based modeling. Appl Environ Microbiol

Modeling Lactococcus lactis using a genome-scale flux model.

Molecular replication.

Morgan JA: Flux balance analysis of photoautotrophic metabolism. Biotechnol Prog

Nutrient-related analyses of pathway/ genome databases. Pac Symp Biocomput

Organization of chemical reactions into dividing and metabolizing units: the chemotons. Biosystems 1975, 7:15-21.Genome Biology

Origin of life: The RNA world. Nature

Palsson BO: Towards a multidimensional genome annotation. Nat Rev Genet

Palsson BØ: A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information. Mol Syst Biol

Palsson BØ: Expanded metabolic reconstruction of Helicobacter pylori (iIT341 GSM/GPR): an in silico genome-scale characterization of single- and doubledeletion mutants.

Palsson BØ: Genome-scale reconstruction of the metabolic network in Staphylococcus aureus N315: an initial draft to the two-dimensional annotation.

Palsson BØ: Investigating the metabolic capabilities of Mycobacterium tuberculosis H37Rv using the in silico strain iNJ661 and proposing alternative drug targets.

PD: MetaCyc: a multiorganism database of metabolic pathways and enzymes. Nucleic Acids Res

PD: MetaCyc: a multiorganism database of metabolic pathways and enzymes. Nucleic Acids Res 2004, 32(Database issue):D438-D442.

Phosphorylation of adenine with yeast enzyme systems [in Hungarian]. Magyar Kémiai Folyóirat

Reconstruction of amino acid biosynthesis pathways from the complete genome sequence. Genome Res

RNA catalysis and the origins of life.

Segrè D: The effect of oxygen on biochemical networks and the evolution of complex life. Science

Separation and characterisation of glycogen synthase kinase 3, glycogen synthase kinase 4 and glycogen synthase kinase 5 from rabbit skeletal muscle.

Shigeoka S: NADPHdependent glutathione peroxidase-like proteins (Gpx-1, Gpx-2) reduce unsaturated fatty acid hydroperoxides

SL: On the origin of metabolic pathways.

Stabilization of energy charge, generation of oscillations and multiple steady states in energy metabolism as a result of purely stoichiometric regulation.

Structural analysis of expanding metabolic networks. Genome Inform

Szathmáry E: Evolutionary potential and requirements for minimal protocells. Topics Curr Chem

TA: Mathematical analysis of multiemzyme systems. II. Steady state and transient control. Biosystems

Tabata S: Sequence analysis of the genome of the unicellular cyanobacterium Synechocystis sp. strain

The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities.

The evolution of replicators.

The membranome and membrane heredity in development and evolution.

The Origin of Life Cambridge:

The Principles of Life (in Hungarian) Budapest: Gondolat;

The Principles of Life Oxford:

The Problems of Life Oxford:

TP: Identification of the Escherichia coli nicotinic acid mononucleotide adenylyltransferase gene.

Vermaas W: In vivo role of catalase-peroxidase

Wiame JM: Arginine metabolism in Saccharomyces cerevisiae: subcellular localization of the enzymes.

https://edit.elte.hu/xmlui/bitstream/10831/92865/1/1443062.pdf

Computational identification of obligatorily autocatalytic replicators embedded in metabolic networks

Abstract

Similar works

Full text

Available Versions

Crossref

ELTE Digital Institutional Repository (EDIT)

Springer - Publisher Connector

Repository of the Academy's Library