Structural organization of biocatalytic systems: the next dimension of synthetic metabolism

In natural metabolic networks, more than 2000 different biochemical reactions are operated and spatially and temporally co-ordinated in a reaction volume of <1 µm3. A similar level of control and precision has not been achieved in chemical synthesis, so far. Recently, synthetic biology succeeded in reconstructing complex synthetic in vitro metabolic networks (SIVMNs) from individual proteins in a defined fashion bottom-up. In this review, we will highlight some examples of SIVMNs and discuss how the further advancement of SIVMNs will require the structural organization of these networks and their reactions to (i) minimize deleterious side reactions, (ii) efficiently energize these networks from renewable energies, and (iii) achieve high productivity. The structural organization of synthetic metabolic networks will be a key step to create novel catalytic systems of the future and advance ongoing efforts of creating cell-like systems and artificial cells.