MoVE identifies metabolic valves to switch between phenotypic states

Abstract

Metabolism is highly regulated, allowing for robust and complex behavior. This behavior can often be achieved by controlling a small number of important metabolic reactions, or metabolic valves. Here, we present a method to identify the location of such valves: the metabolic valve enumerator (MoVE). MoVE uses a metabolic model to identify genetic intervention strategies which decouple two desired phenotypes. We apply this method to identify valves which can decouple growth and production to systematically improve the rate and yield of biochemical production processes. We apply this algorithm to the production of diverse compounds and obtained solutions for over 70% of our targets, identifying a small number of highly represented valves to achieve near maximal growth and production. MoVE offers a systematic approach to identify metabolic valves using metabolic models, providing insight into the architecture of metabolic networks and accelerating the widespread implementation of dynamic flux redirection in diverse systems.