From measurement to implementation of metabolic fluxes

The intracellular reaction rates (fluxes) are the ultimate outcome of the activities of the complete inventory (from DNA to metabolite) and in their sum determine the cellular phenotype. The genotype–phenotype relationship is fundamental in such different fields as cancer research and biotechnology. Here, we summarize the developments in determining metabolic fluxes, inferring major pathways from the DNA-sequence, estimating optimal flux distributions, and how these flux distributions can be achieved in vivo. The technical advances to intervene with the many levels of the cellular architecture allow the implementation of new strategies in for example Metabolic Engineering.

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► In vivo flux distributions can be determined with increasing accuracy and breadth.
► Enzyme activity can partly be identified from codon usage and other DNA features.
► Stoichiometric constraints of metabolism set a frame that can be exploited to design efficient metabolic networks.
► Insights into DNA-sequence–function relationships lead to first examples of rational DNA writing.
► Increasing DNA synthesis speed moves metabolic engineering from tinkering to green field design.