A kinetic model of the central carbon metabolism for acrylic acid production in Escherichia coli

Abstract

Acrylic acid is a value-added chemical used in industry to produce diapers, coatings, paints, and adhesives, among many others. Due to its economic importance, there is currently a need for new and sustainable ways to synthesise it. Recently, the focus has been laid in the use of Escherichia coli to express the full bio-based pathway using 3-hydroxypropionate as an intermediary through three distinct pathways (glycerol, malonyl-CoA, and β-alanine). Hence, the goals of this work were to use COPASI software to assess which of the three pathways has a higher potential for industrial-scale production, from either glucose or glycerol, and identify potential targets to improve the biosynthetic pathways yields. When compared to the available literature, the models developed during this work successfully predict the production of 3-hydroxypropionate, using glycerol as carbon source in the glycerol pathway, and using glucose as a carbon source in the malonyl-CoA and β-alanine pathways. Finally, this work allowed to identify four potential over-expression targets (glycerol-3-phosphate dehydrogenase (G3pD), acetyl-CoA carboxylase (AccC), aspartate aminotransferase (AspAT), and aspartate carboxylase (AspC)) that should, theoretically, result in higher AA yields.

Heterologous Production of Acrylic Acid: Current Challenges and Perspectives

“…In the future, the implementation of other genetic modifications or the use of other enzymes evaluated in other hosts may allow increasing the concentrations. For example, the overexpression of aspartate aminotransferase was predicted to increase in silico the concentrations in E. coli using this route [104], and the same was demonstrated for S. cerevisiae in vivo [40,98]. In addition, the deletion of ldhA, poxB, pta, ackA and/or adhE proved to be beneficial, in general, in the other routes since these deletions allow eliminating competing pathways that deviate pyruvate from the target route.…”

“…Additionally, AA production using E. coli and the glycerol route with 3-HP as an intermediary would probably easily increase by directly supplementing glycerol and by overexpressing the genes from the 3-HP pathway using plasmids instead of integrating these genes in the chassis genome. Moreover, regarding AA production from β-alanine, the overexpression of more genes related to β-alanine accumulation would also help to increase the concentration (e.g., aspartate aminotransferase [40,104], phosphoenolpyruvate carboxylase [46]). Lastly, the elimination of competing pathways (e.g., deletion of yqhD) in the recent study by Zhao et al [105] would also probably allow improving AA production.…”

Changes in the gut microbiome influence the hypoglycemic effect of metformin through the altered metabolism of branched-chain and nonessential amino acids

“…As a result, Escherichia was positively correlated with the hypoglycemic effect. Escherichia could use glucose as a carbon source in the β-alanine pathway [23], and the increase in Escherichia was found to be related to improved glucose homeostasis by the regulation of metabolism, such as carbon uptake, catabolism, and energy and redox production [11,24]. In fact, rats that underwent Roux-en-Y gastric bypass (RYGB) surgery to treat obesity had increased Escherichia and decreased glucose levels.…”

Optimization of chondroitin production inE. coliusing genome scale models

“…Along with the increasing knowledge and data provided by genome sequencing technologies, the number, quality, and applications of available GEMs have been growing. These models provide valuable information for metabolic engineering strategies as they allow to predict phenotypic behavior of either wild-type or mutated strains under different environmental conditions and to identify targets to improve the metabolic flux towards a target product 2,3 . Applications of GEMs on drug target identification/ drug discovery/ drug design and human disease studying have also been described 2 .…”