Computational identification of obligatorily autocatalytic replicators embedded in metabolic networks.
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.


CONCLUSIONS
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.
Kun
Adám
A
Collegium Budapest, Institute for Advanced Study, Szentháromság utca 2, Budapest H-1014, Hungary. kunadam@ludens.elte.hu
Papp
Balázs
B
Szathmáry
Eörs
E
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D002384:Catalysis; D003067:Coenzymes / Q000096:biosynthesis*; D019295:Computational Biology; D004926:Escherichia coli / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D046939:Synechocystis / Q000378:metabolism
D003067:Coenzymes; D000255:Adenosine Triphosphate