Global Transcription Factors Engineering: Rewiring the Transcriptome for Enhanced Biochemical Production

Abstract

For enhanced biochemical production, various metabolic engineering strategies have been developed. Among these, global transcription machinery engineering(gTME) is a promising approach, which engineer a global transcription factor, to reprogram carbon flux toward target products by modulating the metabolic network. In this study, we developed a strategy in which multiple gTFs were engineered simultaneously to maximize diversity of the library by generating variants with rewired metabolic network. To construct the library, we diversified the expression levels of target gTFs by modulating untranslational regeions(UTR) strengths. To evaluate the impact of this strategy on biochemical production, we investigated two target biochemical production. It indicated 66% and 29% increases in both of target biochemicals. These findings suggest that this strategy is an effective strategy for enhancing biochemical production through global transcriptional modulation.