Abstract
Various biosynthetic pathways have been designed to explore sustainable production of glutarate, an attractive C5 building block of polyesters and polyamides. However, its efficient production has not been achieved in Escherichia coli. Here, we use E. coli native lysine catabolic machinery for glutarate biosynthesis. This endogenous genes-only design can generate strong metabolic driving force to maximize carbon flux toward glutarate biosynthesis by replenishing glutamate and NAD(P)H for lysine biosynthesis, releasing lysine feedback inhibition, and boosting oxaloacetate supply. We use native transporters to overcome extracellular accumulation of cadaverine and 5-aminovalerate. With these efforts, both high titer (54.5 g L−1) and high yield (0.54 mol mol−1 glucose) of glutarate production are achieved under fed-batch conditions. This work demonstrates the power of redirecting carbon flux and the role of transporters to decrease intermediate accumulation.
Highlights
Various biosynthetic pathways have been designed to explore sustainable production of glutarate, an attractive C5 building block of polyesters and polyamides
We investigated the effect of dissolved oxygen (DO) on glutarate production
In E. coli, lysine decarboxylation to cadaverine is involved in its adaption to acid stress[38]
Summary
Various biosynthetic pathways have been designed to explore sustainable production of glutarate, an attractive C5 building block of polyesters and polyamides. We use native transporters to overcome extracellular accumulation of cadaverine and 5-aminovalerate With these efforts, both high titer (54.5 g L−1) and high yield (0.54 mol mol−1 glucose) of glutarate production are achieved under fed-batch conditions. Production of adipic acid with high titer (68 g L−1) and yield (0.38 g g−1) has been achieved via a reversal βoxidation pathway[2]. Glutarate is another important dicarboxylic acid used to manufacture polymers such as nylon-4, 5 and nylon-. Reconstructing AMV pathway in a lysine-overproducing E. coli strain resulted in only 0.82 g L−1 of glutarate in shake flasks, representing 9.1% of the theoretical yield (0.75 mol mol−1 glucose)[13]. The possible reasons are that (1) the pathways have unresolved limiting factors preventing carbon flux from reaching the end product and (2) the introduction of the downstream pathway perturbs the existing metabolic balance
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