Designer protein compartments for microbial metabolic engineering.

Protein compartments are distinct structures assembled in living cells via self-assembly or phase separation of specific proteins. Significant efforts have been made to discover their molecular structures and formation mechanisms, as well as their fundamental roles in spatiotemporal control of cellular metabolism. Here, we review the design and construction of synthetic protein compartments for spatial organization of target metabolic pathways toward increased efficiency and specificity. In particular, we highlight the compartmentalization strategies and recent examples to speed up desirable metabolic reactions, to reduce the accumulation of toxic metabolic intermediates, and to switch competing metabolic pathways. We also identify the most important challenges that need to be addressed for exploitation of these designer compartments as a versatile toolkit in metabolic reprogramming. • Compartment formation driven by protein self-assembly or phase transition. • Pathway enzymes can be directed into compartments for metabolic engineering. • Membraneless compartments enable dynamic control of metabolic pathways. • Synthetic protein compartments enable spatial control of cellular metabolism. [ABSTRACT FROM AUTHOR]