Metabolic models and gene essentiality data reveal essential and conserved metabolism in prokaryotes

Abstract

If we tried to list every known chemical reaction within an organismhuman, plant or even bacteriawe would get quite a long and confusing read. But when this information is represented in so-called genome-scale metabolic networks, we have the means to access computationally each of those reactions and their interconnections. Some parts of the network have alternatives, while others are unique and therefore can be essential for growth. Here, we simulate growth and compare essential reactions and genes for the simplest type of unicellular speciesprokaryotesto understand which parts of their metabolism are universally essential and potentially ancestral. We show that similar patterns of essential reactions echo phylogenetic relationships (this makes sense, as the genome provides the building plan for the enzymes that perform those reactions). Our computational predictions correlate strongly with experimental essentiality data. Finally, we show that a crucial step of protein synthesis (tRNA charging) and the synthesis and transformation of small molecules that enzymes require (cofactors) are the most essential and conserved parts of metabolism in prokaryotes. Our results are a step further in understanding the biology and evolution of prokaryotes but can also be relevant in applied studies including metabolic engineering and antibiotic design.