Rewiring microbial metabolism through post-translational switches

Abstract

Recent advances in post-translational regulatory tools have enabled precise and rapid control of metabolic flux in microbial cell factories. In this review, we systematically summarize current post-translational regulatory tools for modulating the abundance, localization, and activity of key metabolic enzymes. We first discuss protein degradation tags for tunable control of enzyme levels. Then, we discuss spatial regulation through natural and synthetic subcellular compartments. We also highlight emerging approaches for engineering allosteric switches, including computational and de novo design methods. Finally, we outline future directions toward orthogonal, efficient, and cross-species compatible systems. This review provides conceptual and technical insights to guide the development of next-generation post-translational regulatory tools for dynamic metabolic control in microbial cell factories.

Keywords: allosteric regulation; metabolic flux control; post-translational regulation; protein degradation tags; subcellular compartmentalization.