Optimization of Large-Scale Production

A hallmark of the synthetic biology is the model-driven development of circuits, chassis and processes. We will link and embed the dynamic model of central metabolism into a whole-cell constraint-based framework. By incorporating the dynamic metabolic model, we will be able to study the effects of synthetic gene circuits designed to increase growth of M. pneumoniae. Furthermore, we will use the model to identify and test new medium components that could enhance growth rate. The model will be experimentally validated in dedicated bioreactor growth experiments under defined sets of conditions. Measurement of well-chose fluxes will allow capturing the main metabolic features. We will use the genome-scale metabolic models developed to algorithmically generate minimal media “candidate” formulations. We will deploy a series of constraint-based analysis methods to systematically query and ascertain possible flux distributions and genetic construction that can possibly lead to improved growth rates without loss of the other desired functions. The ranked configurations will be assessed under a number of criteria for fitness, feasibility, gain, etc. for subsequent implementation.