Toward Design Principles for Biomolecular Condensates for Metabolic Pathways.

Biology uses membrane-less organelles or biomolecular condensates as dynamic reaction compartments that can form or dissolve to regulate biochemical pathways. This has led to a flurry of research aiming to design new synthetic organelles that function as reaction crucibles for enzymes and biomolecular cascades in biotechnology. The mechanisms by which a condensate can enhance multistep biochemical processes including mass action, tuning the chemical environment, scaffolding and metabolic channelling is reviewed. These mechanisms are not inherently beneficial for the rate of enzymatic processes but can also inhibit a reaction. Similarly, some aspects of condensates are likely intrinsically inhibitory including retardation of diffusion, where the net effect of a condensate will be a trade-off between inhibitory and stimulatory effects. It is discussed which generalizable conclusions can be drawn so far and how close it is to design principles for condensates for enzyme cascades in microbial cell factories including which reactions are likely to be enhanced by condensates and which type of condensate will be suited for which reaction.