Engineering static and dynamic control of microbial biosynthetic pathways in escherichia coli
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In metabolic engineering, control of native metabolism is significant when optimizing strains for overproduction of the desired compounds in the selected host strains. However, for many central metabolic pathway genes, static knockout strategies result in poor cell growth and gene expression. To address this problem, we have engineered antisense RNAs to achieve conditionally static repression of multiple genes in fatty acid biosynthesis pathway to increase the malonyl-CoA pool and improve the bioproduction of malonyl-CoA-derived compounds. Inspired from naturally-existed dynamic regulatory systems, we engineered an artificial dynamic control network to dynamically regulate the exogenous pathways and the endogenous metabolic network in an orthogonal manner, permitting maximum utilization of carbon source. Furthermore, we anchored this dynamic control system into the muconic acid (MA) biosynthesis pathway to test its applicability. This research provided a proof-of concept demonstrating static and dynamic control of the gene expression, enriched new yield optimization approvals and supplied a theoretical basis for biosynthesis research.