Systems analysis of metabolic phenotypes: what have we learnt?

• Metabolic flux analysis and modeling generates a network view of metabolism.
• The nature of inputs and demand for outputs substantially influences the metabolic flux phenotype.
• Tools are beginning to be used that afford greater spatiotemporal resolution of the metabolic phenotype.
• In silico analysis of plant metabolism can shape metabolic engineering strategies.

Flux is one of the most informative measures of metabolic behavior. Its estimation requires integration of experimental and modeling approaches and, thus, is at the heart of metabolic systems biology. In this review, we argue that flux analysis and modeling of a range of plant systems points to the importance of the supply of metabolic inputs and demand for metabolic end-products as key drivers of metabolic behavior. This has implications for metabolic engineering, and the use of in silico models will be important to help design more effective engineering strategies. We also consider the importance of cell type-specific metabolism and the challenges of characterizing metabolism at this resolution. A combination of new measurement technologies and modeling approaches is bringing us closer to integrating metabolic behavior with whole-plant physiology and growth.