title: Remnants of an Ancient Metabolism without Phosphate.
abstract: Phosphate is essential for all living systems, serving as a building block of genetic and metabolic machinery. However, it is unclear how phosphate could have assumed these central roles on primordial Earth, given its poor geochemical accessibility. We used systems biology approaches to explore the alternative hypothesis that a protometabolism could have emerged prior to the incorporation of phosphate. Surprisingly, we identified a cryptic phosphate-independent core metabolism producible from simple prebiotic compounds. This network is predicted to support the biosynthesis of a broad category of key biomolecules. Its enrichment for enzymes utilizing iron-sulfur clusters, and the fact that thermodynamic bottlenecks are more readily overcome by thioester rather than phosphate couplings, suggest that this network may constitute a "metabolic fossil" of an early phosphate-free nonenzymatic biochemistry. Our results corroborate and expand previous proposals that a putative thioester-based metabolism could have predated the incorporation of phosphate and an RNA-based genetic system. PAPERCLIP.
authors.affiliation: Bioinformatics Program, Boston University, Boston, MA 02215, USA.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Goldford
authors.affiliation: Earth, Atmosphere and Planetary Science Department, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Hyman
authors.initials: H
authors.lastname: Hartman
authors.affiliation: Bioinformatics Program, Boston University, Boston, MA 02215, USA; Department of Biomedical Engineering, Boston University, Boston MA, 02215, USA.
authors.forename: Temple F
authors.initials: TF
authors.lastname: Smith
authors.affiliation: Bioinformatics Program, Boston University, Boston, MA 02215, USA; Department of Biomedical Engineering, Boston University, Boston MA, 02215, USA; Department of Biology, Department of Physics, Boston University, Boston MA, 02215, USA. Electronic address: dsegre@bu.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Segrè
mesh_terms: D000227:Adenine Nucleotides / Q000737:chemistry; D000465:Algorithms; D003065:Coenzyme A; D003067:Coenzymes; D003198:Computer Simulation; D053858:Metabolic Networks and Pathways; D000069497:Origin of Life; D010710:Phosphates / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D000227:Adenine Nucleotides; D003067:Coenzymes; D010710:Phosphates; D003065:Coenzyme A
keywords: network expansion; origin of life; phosphate; systems biology; thioester world