Harnessing the hierarchy of transcriptional regulation: engineering of the gene expression network for efficient production

Abstract The biosynthetic pathway is embedded in complex genetic background of the host cells. To achieve efficient production, the expression of the host genes and the targeted synthetic pathways has to be coordinated to channel the resources from basic metabolism to biosynthesis. The gene expression profile is governed by a cascade of regulations, among which the transcriptional regulation basically determines the final phenotype. Transcriptional regulation also works in a hierarchical manner, and as the level of regulation escalates, the regulatory capacity increases from single to multiple targets, so as the impact on global gene expression. This chapter first lays the background by introducing the components of the transcription machinery and the structure of the transcriptional regulatory network. Strategies to enhance the performance of the biosynthetic pathway through transcriptional regulation are categorized and analyzed by their levels of regulation in the network. In conclusion, reconstructing gene expression profile at the global network-level holds the promise to achieve efficient and robust biosynthesis.