Combinatorial UTR Engineering of Global Transcription Factors Enables Transcriptome Rewiring 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 engineers a global transcription factor, to reprogram carbon flux toward target products by modulating the metabolic network. In this study, we simultaneously engineered multiple gTFs to maximize the 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 untranslated regeions(UTRs) strengths. To evaluate the effect of our strategy on biochemical production, we investigated free fatty acids (FFAs) and polyhydroxybutyrate (PHB) production. It resulted high increases in FFAs and PHB production, respectively. These findings suggest that our approach is an effective strategy for enhancing biochemical production through global transcriptional modulation.