(449c) Cascaded Dynamic Regulation for Attenuated Metabolic Imbalance and Increased Naringenin Production

The conflicts between cell growth and production often hinder the development of efficient microbial cell factories for the biosynthesis of valuable compounds. Dynamic regulation becomes an efficient approach to relieve the conflicts as it can redirect the carbon fluxes to target production based on cellular status or environmental signals. Naringenin is a valuable natural product with antibacterial, antifungal, and antiviral properties. However, the synthetic pathway of naringenin suffers from the low productivities arising from the imbalance of carbon flux and enzyme expression. Here, we presented a cascaded dynamic regulation system to systematically optimize the naringenin biosynthesis in Escherichia coli. The implementation of the cascaded dynamic regulation effectively attenuated the cell burdens and waste of resources caused by constitutive enzyme overexpression, resulting an over 23-fold increase in naringenin titer compared with the original strain. Our results highlighted the great potential of multi-level cascaded dynamic regulation in metabolic engineering.