Abstract
Water, the most abundant compound on the surface of the Earth and probably in the universe, is the medium of biology, but is much more than that. Water is the most frequent actor in the chemistry of metabolism. Our quantitation here reveals that water accounts for 99.4% of metabolites in Escherichia coli by molar concentration. Between a third and a half of known biochemical reactions involve consumption or production of water. We calculated the chemical flux of water and observed that in the life of a cell, a given water molecule frequently and repeatedly serves as a reaction substrate, intermediate, cofactor, and product. Our results show that as an E. coli cell replicates in the presence of molecular oxygen, an average in vivo water molecule is chemically transformed or is mechanistically involved in catalysis ~ 3.7 times. We conclude that, for biological water, there is no distinction between medium and chemical participant. Chemical transformations of water provide a basis for understanding not only extant biochemistry, but the origins of life. Because the chemistry of water dominates metabolism and also drives biological synthesis and degradation, it seems likely that metabolism co-evolved with biopolymers, which helps to reconcile polymer-first versus metabolism-first theories for the origins of life.