Reconstructing the transcription regulatory network to optimize resource allocation for robust biosynthesis

An ideal microbial cell factory (MCF) should deliver maximal resources to production, which conflicts with the microbe's native growth-oriented resource allocation strategy and can therefore lead to early termination of the high-yield period. Reallocating resources from growth to production has become a critical factor in constructing robust MCFs. Instead of strengthening specific biosynthetic pathways, emerging endeavors are focused on rearranging the gene regulatory network to fundamentally reprogram the resource allocation pattern. Combining this idea with transcriptional regulation within the hierarchical regulatory network, this review discusses recent engineering strategies targeting the transcription machinery, module networks, regulatory edges, and bottom network layer. This global view will help to construct a production-oriented phenotype that fully harnesses the potential of MCFs.