Tunable hybrid carbon metabolism coordination for the carbon-efficient biosynthesis of 1,3-butanediol in Escherichia coli?

Green Chemistry Pub Date: 2021-10-04 DOI: 10.1039/D1GC02867G

Abstract

Microbial-based bio-refining seeks to replace fossil-based chemical industry with reduced capital cost and lower environmental concern. However, current metabolic engineering practices suffer from intensive CO2 emission and limited yield ceiling via hardwired native biochemical infrastructures. Herein, via a highly-efficient 1,3-butanediol pathway, we demonstrate a new approach of tunable hybrid carbon metabolism coordination for carbon-efficient bioproduction in engineered Escherichia coli. The approach fine-tunes a phosphoketolase-mediated non-oxidative glycolysis based on computational analysis to accommodate the output NAD(P)H/acetyl-CoA stoichiometries from sugar breakdown to downstream pathway demands, raising the theoretical pathway yields of acetyl-CoA-derived products to their upper limits. As a proof-of-concept demonstration, coordination of hybrid carbon metabolism enables the highest titer to date of 3-hydroxybutyrate from glucose (51.13 g l?1) in bioreactor-based fed-batch cultivation, with a yield (1.13 mol mol?1) reaching 113% of the theoretical maximum from native metabolism. Further combination of carbon metabolism coordination and a novel 3-hydroxybutyrate-responsive dynamic control circuit for fatty acid pathway repression affords the highest titer and yield to date of 1,3-butanediol (22.66 g l?1, 0.80 mol mol?1) from glucose. This work demonstrates a generalizable approach for carbon-efficient microbial production through a hybrid and tunable biochemical infrastructure.

Graphical abstract: Tunable hybrid carbon metabolism coordination for the carbon-efficient biosynthesis of 1,3-butanediol in Escherichia coli
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