Developing a pyruvate-driven metabolic scenario for growth-coupled microbial production

Abstract

Microbial-based chemical synthesis serves as a promising approach for sustainable production of industrially important products. However, limited production performance caused by metabolic burden or genetic variations poses one of the major challenges in achieving an economically viable biomanufacturing process. To address this issue, one superior strategy is to couple the product synthesis with cellular growth, which renders production obligatory for cell survival. Here we create a pyruvate-driven metabolic scenario in engineered Escherichia coli for growth-coupled bioproduction, with which we demonstrate its application in boosting production of anthranilate and its derivatives. Deletion of a minimal set of endogenous pyruvate-releasing pathways engenders anthranilate synthesis as the salvage route for pyruvate generation to support cell growth, concomitant with simultaneous anthranilate production. Further introduction of native and non-native downstream pathways affords production enhancement of two anthranilate-derived high-value products including L-tryptophan and cis, cis-muconic acid from different carbon sources. The work reported here presents a new growth-coupled strategy with demonstrated feasibility for promoting microbial production.

Keywords: Anthranilate; Growth coupling; Metabolic engineering; Pyruvate-driven system.