Simplified metabolic pathway design for efficient production in halotolerant microbial systems.

Halotolerant microorganisms are promising cell factories for industrial biomanufacturing because they combine physiological robustness with practical advantages, including contamination-resistant fermentation, reduced sterilization requirements, and compatibility with saline feedstocks. However, the metabolic burden of stress adaptation, together with regulatory redundancy and pathway complexity, often limits production efficiency and genetic stability. Simplified metabolic pathway design has therefore emerged as a key strategy to improve halotolerant cell factories. Here, we review recent advances from three complementary perspectives: simplified chassis construction through genome streamlining and deletion of competing pathways; simplified pathway design through modularization and orthogonalization; and enabling tools, including genetic transformation, multiplex genome editing, dynamic regulation, evolutionary and computational approaches. Together, these developments define a conceptual and practical framework for rational simplification of halotolerant metabolism, providing design principles for both current industrial hosts and emerging extremophilic chassis.