(449b) Utilizing Antimicrobial Peptide for Regulation of Global Metabolism and Its Application in Microbial Biosynthesis

Maintaining proper balance between cell growth and target product biosynthesis is a fundamental challenge for metabolic engineering. In this study, we utilize a robust antimicrobial peptide (AMP) to block protein synthesis and thus repress the global metabolism of model bacterium E. coli at desired timings, which directs metabolic resources towards the target product biosynthesis. Our results show that, through manipulating the growth conditions (e.g., medium composition), the selected AMP is able to inhibit the cell growth to varied degrees. The induction of AMP expression at different time points during the cell growth also leads to different growth inhibition outcomes, ranging from dramatic to unnoticeable growth freeze. On the other hand, the biosynthesis of a selected target product in the AMP-containing E. coli can be engineered to be impacted to a lesser degree by the AMP expression. Thus, the distribution of the metabolic resources between cell growth and target product production can be manipulated through controlled AMP expression. We further explore the use of this strategy for enhancing the biosynthesis of selected products in engineered E. coli for facilitating its application in metabolic engineering.