Compatibility engineering of synthetic metabolic pathways in microbial cell factories

Microbial cell factories employ tailored synthetic pathways to produce diverse valuable compounds efficiently and sustainably. However, mismatches between engineered pathways and the chassis often compromise pathway performance and undermine overall stability and productivity. In this review, we analyze the origins of compatibility issues and propose a framework and methods for compatibility engineering, encompassing both hierarchical and global compatibility engineering. Furthermore, we discuss the remaining challenges and future directions for ensuring seamless integration of synthetic metabolic pathways within microbial hosts.