PT - JOURNAL ARTICLE
AU - de Groot, Daan Hugo
AU - PlanquÃ©, Robert
AU - van Boxtel, Coco
AU - Bruggeman, Frank J.
AU - Teusink, Bas
TI - Maximal growth rate requires minimal metabolic complexity
DP - 2017 Jan 01
TA - bioRxiv
4099 - http://biorxiv.org/content/early/2017/07/21/167171.short
4100 - http://biorxiv.org/content/early/2017/07/21/167171.full
AB - The rate at which a microorganism produces offspring (specific growth rate) is a near universal selective pressure across microbial species. Growth requires metabolic enzymes, whose properties and expressions are moulded by evolution, within the bounds set by physical and chemical constraints. We asked therefore, if basic (bio)chemistry can determine the outcome of evolution. We found an evolutionary extremum principle that dictates that specific growth rate maximisation requires minimisation of metabolic complexity. This principle is a mathematical consequence of maximising specific growth rate under mass-conservation and protein-concentration constraints. We prove that the number of growth-limiting constraints bounds the number of active metabolic subnetworks (defined by Elementary Flux Modes) at maximal growth rate. Therefore, the complexity of metabolic behaviour is determined by the number of active protein constraints, not the size of the network. The consequences of the fundamental principle can be visualised in a graphical framework that provides a unified understanding of metabolic behaviours conserved across microbial species, such as diauxic growth, mixed substrate usage and overflow metabolism. This work therefore provides a biochemical basis for the fundamental limits of evolution, and the driving forces of evolutionary change under growth-enabling conditions.