Recent Progress in Metabolic Engineering of Escherichia coli for the Production of Various C4 and C5-Dicarboxylic Acids

Abstract

As an alternative to petrochemical synthesis, well-established industrial microbes, such as Escherichia coli, are employed to produce a wide range of chemicals, including dicarboxylic acids (DCAs), which have significant potential in diverse areas including biodegradable polymers. The demand for biodegradable polymers has been steadily rising, prompting the development of efficient production pathways on four-(C4) and five-carbon (C5) DCAs derived from central carbon metabolism to meet the increased demand via the biosynthesis. In this context, E. coli is utilized to produce these DCAs through various metabolic engineering strategies, including the design or selection of metabolic pathways, pathway optimization, and enhancement of catalytic activity. This review aims to highlight the recent advancements in metabolic engineering techniques for the production of C4 and C5 DCAs in E. coli.

Application of functional genomics for domestication of novel non-model microbes

“…Realizing the industrial potential of these microbes will require rapid development of amenable genetic tools. As it currently stands, there is a lack of broadly applicable genetic tools, including selectable markers, promoters, plasmid origins, and transformation protocols, as broadly utilized mesophilic tools are not functional in these thermophilic microbes (Y. Wang et al., 2024 ; Ye et al., 2023 ). While there are a growing number of tools being generated for use in thermophilic microbes (Adalsteinsson et al., 2021 ; Le & Sun, 2022 ; Riley et al., 2019 ; Walker et al., 2020 ; Wang et al., 2022 ; Wu et al., 2023 ; Yang et al., 2023 ), developing new tools and implementing CRISPR mediated genome engineering and/or thermostable serine recombinase-assisted genome engineering (SAGE) mediated integration would greatly simplify testing production of various industrial chemicals in these currently underutilized microbes (Fenster & Eckert, 2021 ; Wu et al., 2023 ).…”

Flipping the switch: dynamic modulation of membrane transporter activity in bacteria

“…Application of this information could have multiple uses in actively modulating cellular function. Some will serve as excellent drug targets, but the tendency for bacteria to build redundancy into their small molecule transporters means that in many cases they will not be suitable targets [159]; however, their manipulation during biotechnological processes to limit the flow of a nutrient and/or product in or out of the cell is certainly possible, although to date examples of 'transporter engineering' sit around changing transporter profiles through manipulating gene expression rather than protein activity [160][161][162]. We hope this review serves as a useful summary of what is known and act as a catalyst for more study in this area.…”

Biotechnological Valorization of Waste Glycerol into Gaseous Biofuels—A Review

“…Thus, interventions are needed to modify and increase the efficiency of natural enzymes and accelerate metabolic pathways to maximize industrial benefits [14]. Process improvement draws on research regarding metabolic engineering, genetic modification, and upgrading/optimization current processes [15,16]. The most common refinements include: eliminating transcriptional repression and inhibiting enzyme feedback; reducing the generation and accumulation of undesired by-products in the medium; enhancing and improving the medium via micro-nutrient amendment; reducing energy consumption and cost of the system; expanding the substrate and end product portfolio; and enhancing strain tolerance to inhibitors and environmental stress [17,18].…”