Wiring cell growth to product formation

A diverse library of producers is characterized for production variants. Suitable selection systems allow growth only above the threshold, reducing the original library to the top producers. [Display omitted] •Selections offer highest throughput for interrogation of biological diversity and optimization of cell factories.•Traditional selection systems are complemented by computational and synthetic biology.•Synthetic selection systems are subject to escape via detrimental mutations.•Redundant selection systems or positive and negative selections can reduce escape rates dramatically. Microbial cell factories offer new and sustainable production routes for high-value chemicals. However, identification of high producers within a library of clones remains a challenge. When product formation is coupled to growth, millions of metabolic variants can be effectively interrogated by growth selection, dramatically increasing the throughput of strain evaluation. While growth-coupled selections for cell factories have a long history of success based on metabolite auxotrophies and toxic antimetabolites, such methods are generally restricted to molecules native to their host metabolism. New synthetic biology tools offer the opportunity to rewire cellular metabolism to depend on specific and non-native products for growth.