The Role Of Prebiotic Phosphate In The Origin Of Metabolic Network

The origin of life is one of the most important and challenging issues in the natural sciences.Phosphorus is essential for modern life,and is considered to plays an important role in the origin of life.However,recently,Goldford et al.constructed a phosphate-free metabolic network and proposed an unconventional new view: metabolism can originate without phosphorus.This view prompted us to re-examine the role of phosphorus in the origin of metabolism.Therefore,based on the previous researches,the current study will comprehensively explore the role of phosphorus in the origin of metabolic networks and provides deeper insights into the origin of life.1.Construction of ancient metabolic networksFirstly,a phosphorus-independent protometabolic network was reconstructed with the latest KEGG metabolic reaction data using the network expansion simulation algorithm.The resulting network contains almost all of the reactions of the network constructed by Goldford et al..This result validated the reliability of the data and the method.To explore the role of phosphorus in the origin of metabolism,phosphorus-dependent protometabolic networks were constructed using the same methed with seed sets containing different prebiotically available phosphates.The obtained phosphorus-dependent metabolic networks were composed of the same reactions,implying that the network was robust to different phosphorus sources.2.Ancient origin of phosphorus-dependent metabolic networkSecondly,the ancient origin of the phosphorus-dependent metabolic network was verified by bioinformatics and chemical informatics methods.The enrichment of the last universal common ancestor(LUCA)-related features which observed in the phosphorus-dependent network implied that a great portion of the reactions in this network also existed in the earliest life.The origins of the enzymes participating in the networks were traced by the protein-domain structure-based molecular clocks.This analysis showed that phosphorus-dependent and-independent metabolic networks originated at the same evolutionary stage.By analyzing the chemical characteristics of the phosphorus-dependent and-independent networks,it was found that metabolites in the two networks have higher water solubility,stronger molecular polarity,and smaller molecular weight than modern metabolites.Taken together,the phosphorus-dependent metabolic network exhibits critical ancient characters,both phosphorus-dependent and-independent network have an ancient origin.3.Metabolic network expansion by prebiotic phosphatesThen,the influence of phosphates on the protometabolic network was studied by the KEGG pathway enrichment analysis of the KEGG metabolic pathway.We found that phosphates promote carbon metabolism as well as carbohydrate metabolism.These metabolic pathways are extremely important for sustaining energy flow in modern life and for the formation of the RNA world.In addition,the presence of phosphorus also promotes the production of complex metabolites and enhanced the diversity of metabolites.4.Thermodynamic bottleneck alleviation by prebiotic phosphatesFinally,the effect of phosphate on thermodynamic property of the prebiotic protometabolic network was investigated using thermodynamically constrained network expansion simulation algorithm.Glycolytic is generally considered to be a possible important energy source for the ancient life.So perbiotic available high-energy phosphorylation intermediates of glycolytic pathway,such as glucose 6-phosphate,fructose 6-phosphate,fructose 1,6-bisphosphate,glyceraldehyde 3-phosphate,glycerate 2-phosphate,glycerate 3-phosphate,and phosphoenolpyruvate,were used for simulation in this study.These results showed that phosphates can effectively reduce thermodynamic bottlenecks and promote the expansion of the metabolic network.In summary,our research demonstrates that i)the phosphorous-dependent metabolism could originate in very early stage of biochemical processes;ii)phosphorus can promote reactions which are essential for life;iii)some high-energy phosphates can ensure the prebiotic metabolism under feasible energetic constraints.These results revealed the important roles of phosphorous played in the prebiotic metabolism,and provided deeper insights into the origin of life.