Feedback regulation and coordination of the main metabolism for bacterial growth and metabolic engineering for amino acid fermentation

Living organisms such as bacteria are often exposed to continuous changes in the nutrient availability in nature. Therefore, bacteria must constantly monitor the environmental condition, and adjust the metabolism quickly adapting to the change in the growth condition. For this, bacteria must orchestrate (coordinate and integrate) the complex and dynamically changing information on the environmental condition. In particular, the central carbon metabolism (CCM), monomer synthesis, and macromolecular synthesis must be coordinately regulated for the efficient growth. It is a grand challenge in bioscience, biotechnology, and synthetic biology to understand how living organisms coordinate the metabolic regulation systems. Here, we consider the integrated sensing of carbon sources by the phosphotransferase system (PTS), and the feed-forward/feedback regulation systems incorporated in the CCM in relation to the pool sizes of flux-sensing metabolites and αketoacids. We also consider the metabolic regulation of amino acid biosynthesis (as well as purine and pyrimidine biosyntheses) paying attention to the feedback control systems consisting of (fast) enzyme level regulation with (slow) transcriptional regulation. The metabolic engineering for the efficient amino acid production by bacteria such as Escherichia coli and Corynebacterium glutamicum is also discussed (in relation to the regulation mechanisms). The amino acid synthesis is important for determining the rate of ribosome biosynthesis. Thus, the growth rate control (growth law) is further discussed on the relationship between (p)ppGpp level and the ribosomal protein synthesis.