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 a… Show more
“…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.…”
Section: β-Alanine Routementioning
confidence: 83%
“…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.…”
Section: Key Points To Optimize Aa Heterologous Productionmentioning
Acrylic acid (AA) is a chemical with high market value used in industry to produce diapers, paints, adhesives and coatings, among others. AA available worldwide is chemically produced mostly from petroleum derivatives. Due to its economic relevance, there is presently a need for innovative and sustainable ways to synthesize AA. In the past decade, several semi-biological methods have been developed and consist in the bio-based synthesis of 3-hydroxypropionic acid (3-HP) and its chemical conversion to AA. However, more recently, engineered Escherichia coli was demonstrated to be able to convert glucose or glycerol to AA. Several pathways have been developed that use as precursors glycerol, malonyl-CoA or β-alanine. Some of these pathways produce 3-HP as an intermediate. Nevertheless, the heterologous production of AA is still in its early stages compared, for example, to 3-HP production. So far, only up to 237 mg/L of AA have been produced from glucose using β-alanine as a precursor in fed-batch fermentation. In this review, the advances in the production of AA by engineered microbes, as well as the hurdles hindering high-level production, are discussed. In addition, synthetic biology and metabolic engineering approaches to improving the production of AA in industrial settings are presented.
“…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.…”
Section: β-Alanine Routementioning
confidence: 83%
“…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.…”
Section: Key Points To Optimize Aa Heterologous Productionmentioning
Acrylic acid (AA) is a chemical with high market value used in industry to produce diapers, paints, adhesives and coatings, among others. AA available worldwide is chemically produced mostly from petroleum derivatives. Due to its economic relevance, there is presently a need for innovative and sustainable ways to synthesize AA. In the past decade, several semi-biological methods have been developed and consist in the bio-based synthesis of 3-hydroxypropionic acid (3-HP) and its chemical conversion to AA. However, more recently, engineered Escherichia coli was demonstrated to be able to convert glucose or glycerol to AA. Several pathways have been developed that use as precursors glycerol, malonyl-CoA or β-alanine. Some of these pathways produce 3-HP as an intermediate. Nevertheless, the heterologous production of AA is still in its early stages compared, for example, to 3-HP production. So far, only up to 237 mg/L of AA have been produced from glucose using β-alanine as a precursor in fed-batch fermentation. In this review, the advances in the production of AA by engineered microbes, as well as the hurdles hindering high-level production, are discussed. In addition, synthetic biology and metabolic engineering approaches to improving the production of AA in industrial settings are presented.
“…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.…”
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“…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 .…”
Chondroitin is a natural occurring glycosaminoglycan with applications as a nutraceutical and pharmaceutical ingredient and can be extracted from animal tissues. Microbial chondroitin-like polysaccharides emerged as a safer and more sustainable alternative source. However, chondroitin titers using either natural or recombinant microorganisms are still far from meeting the increasing demand. The use of genome-scale models and computational predictions can assist the design of microbial cell factories with possible improved titers of these value-added compounds. Genome-scale models have been used to predict genetic modifications inEscherichia coliengineered strains that would potentially lead to improved chondroitin production. Additionally, using synthetic biology approaches, a pathway for producing chondroitin has been designed and engineered inE. coli. Afterwards, the most promising mutants identified based on bioinformatics predictions were constructed and evaluated for chondroitin production in flask fermentation. This resulted in the production of 118 mg/L of extracellular chondroitin by overexpressing both superoxide dismutase (sodA) and a lytic murein transglycosylase (mltB). Then, batch and fed-batch fermentations at bioreactor scale were also evaluated, in which the mutant overexpressingmltBled to an extracellular chondroitin production of 427 mg/L and 535 mg/L, respectively. The computational approach herein described identified several potential novel targets for improved chondroitin biosynthesis, which may ultimately lead to a more efficient production of this glycosaminoglycan.
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