The Impact of Oxygen on Metabolic Evolution: A Chemoinformatic Investigation

Abstract

The appearance of planetary oxygen likely transformed the chemical and biochemical makeup of life and probably triggered episodes of organismal diversification. Here we use chemoinformatic methods to explore the impact of the rise of oxygen on metabolic evolution. We undertake a comprehensive comparative analysis of structures, chemical properties and chemical reactions of anaerobic and aerobic metabolites. The results indicate that aerobic metabolism has expanded the structural and chemical space of metabolites considerably, including the appearance of 130 novel molecular scaffolds. The molecular functions of these metabolites are mainly associated with derived aspects of cellular life, such as signal transfer, defense against biotic factors, and protection of organisms from oxidation. Moreover, aerobic metabolites are more hydrophobic and rigid than anaerobic compounds, suggesting they are better fit to modulate membrane functions and to serve as transmembrane signaling factors. Since higher organisms depend largely on sophisticated membrane-enabled functions and intercellular signaling systems, the metabolic developments brought about by oxygen benefit the diversity of cellular makeup and the complexity of cellular organization as well. These findings enhance our understanding of the molecular link between oxygen and evolution. They also show the significance of chemoinformatics in addressing basic biological questions.

Author Summary

Elucidating the link between the rise of planetary oxygen and biological evolution is a challenging topic in evolutionary biology. Previous studies in this area were dominated by biological investigations. The recent simulations of metabolic networks under anaerobic or aerobic conditions revealed that aerobic metabolism gave rise to 1,000+ new reactions. Since metabolites are small molecules and metabolic reactions are basically chemical reactions, we think that the impact of oxygen on metabolic evolution can be well studied by chemoinformatics. In this paper, we use chemoinformatic methods to perform a comprehensive comparative analysis of the chemical structures, properties and reactions of anaerobic and aerobic metabolites. It was found that aerobic metabolism has considerably expanded the structural space of metabolites by inventing 130 novel molecular scaffolds. Moreover, aerobic metabolism also helped organisms to explore a new chemical space by increasing the hydrophobicity and rigidity of metabolites. Since hydrophobic metabolites are fitting to modulate membrane functions and to serve as transmembrane signaling factors, these metabolic innovations definitely benefit the establishment of complex cellular organizations. The present findings not only help to understand the molecular link between oxygen and evolution but also suggest that chemoinformatics is of special value in addressing some basic biological questions.