Genetic manipulation of Escherichia coli central carbon metabolism for efficient production of fumaric acid

Liu, Huan; Song, Ruirui; Yue, Liang; Zhang, Ting; Deng, Li; Wang, Fang; Tan, Tianwei

doi:10.1016/j.biortech.2018.08.024

Cited by 27 publications

(19 citation statements)

References 31 publications

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“…Metabolic engineering is conducted to rewire the complete noncyclic glyoxylate pathway for fumarate production. Recently, five metabolic engineering strategies have been developed to enhance production of fumarate: reconstructing synthetic pathway, such as the reductive TCA cycle [ 2 ], the oxidative TCA cycle [ 3 ], the noncyclic glyoxylate cycle [ 4 ], the urea cycle and the purine nucleotide cycle [ 27 , 28 ]; eliminating byproducts formation [ 27 ], such as lactate, acetate, formate, malate, and succinate; optimizing oxidation and reduction levels [ 5 ]; modifying glucose transport system [ 8 ]; regulating C 4 -dicarboxylate transporter [ 26 ]. These results indicated that fumarate production has been improved by metabolic engineering strategies.…”

Section: Discussionmentioning

confidence: 99%

“…Pathway optimization represents one significant step in identifying and removing the potential bottlenecks to improve the transmission efficiency of biosynthetic pathway. To improve the transmission efficiency of intermediate metabolites, the partial noncyclic glyoxylate pathway was constructed by replacing the native PEP-dependent PTSG system with the PEP-independent galactose translocation system, overexpressing phosphoenolpyruvate carboxylase (PPC) and acetyl-CoA synthase, and deleting malate dehydrogenase, fumarate reductase, and fumarase [ 8 ]. The final concentration of fumarate (1.53 g/g dry cell weight) was increased by 50% compared with the parental strain.…”

Section: Discussionmentioning

confidence: 99%

“…As for the noncyclic glyoxylate cycle, the maximum theoretical yield of fumarate is 1 mol/mol glucose. Although this pathway has shown its promising applications in improving the productivity of carboxylic acids [ 7 ], only few studies have focused on this pathway for fumarate production [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Engineering the transmission efficiency of the noncyclic glyoxylate pathway for fumarate production in Escherichia coli

Chen

Liu

et al. 2020

Biotechnol Biofuels

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Background Fumarate is a multifunctional dicarboxylic acid in the tricarboxylic acid cycle, but microbial engineering for fumarate production is limited by the transmission efficiency of its biosynthetic pathway. Results Here, pathway engineering was used to construct the noncyclic glyoxylate pathway for fumarate production. To improve the transmission efficiency of intermediate metabolites, pathway optimization was conducted by fluctuating gene expression levels to identify potential bottlenecks and then remove them, resulting in a large increase in fumarate production from 8.7 to 16.2 g/L. To further enhance its transmission efficiency of targeted metabolites, transporter engineering was used by screening the C 4 -dicarboxylate transporters and then strengthening the capacity of fumarate export, leading to fumarate production up to 18.9 g/L. Finally, the engineered strain E. coli W3110△4-P (H) CAI (H) SC produced 22.4 g/L fumarate in a 5-L fed-batch bioreactor. Conclusions In this study, we offered rational metabolic engineering and flux optimization strategies for efficient production of fumarate. These strategies have great potential in developing efficient microbial cell factories for production of high-value added chemicals.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Engineering the transmission efficiency of the noncyclic glyoxylate pathway for fumarate production in Escherichia coli

Chen

Liu

et al. 2020

Biotechnol Biofuels

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“…A high-performance liquid chromatograph (HPLC; Shimadzu Corporation, Kyoto, Japan) equipped with a refractive index detector and UV detector (210 nm) was utilized to detect the titer of fumaric acid, by-product ethanol, and glucose consumption. The column used was a Bio-Rad Aminex HPX-87 H ion exclusion column (Richmond, CA, USA), and 0.005 M H2SO4 was used as eluent at 50 ℃ with a flow rate of 0.6 mL/min (Liu et al 2018a). Due to the low solubility of fumaric acid and calcium fumarate, both accumulated as precipitated in the broth.…”

Section: Methodsmentioning

confidence: 99%

Applications of one-Step environmentally-friendly fermentation method to produce fumaric acid with immobilized Rhizopus arrhizus in stirred-tank reactor

Ning

Yang

Zhao

et al. 2021

BioRes

Self Cite

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The traditional two-step cultivation mode for fungal cultivation is commonly divided into the seed stage (usually 24 to 48 h) and the production stage (usually 96 to 144 h). The use of two stages prolongs the total production cycle and generates excess wastewater. In this work, an efficient and environmentally friendly one-step fermentation method was applied for the production of fumaric acid by immobilized Rhizopus arrhizus in a stirred-tank reactor. The nitrogen source content and the agitation speed of the reactor were optimized as the two critical factors in the one-step fermentation process; the fumaric acid production of 51 g/L with a yield of 0.42 g/g glucose was comparable with the product from the traditional two-step fermentation process. Furthermore, the total production cycle was shortened to 96 h, and the amount of wastewater was reduced due to the avoidance of the seed culture process. Thus, utilization of the one-step fermentation method to produce fumaric acid was shown to be preferable feasibility and environmental-friendliness. This is a promising method for industrial production of fumaric acid and other high-value biochemicals by fungus.

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“…This strategy helped to achieve the best yield (1.53 g/g dcw) is 50% higher compared to the parental strain. For the modifications in E. Coli , PEP‐dependent glucose phosphotransferase enzyme groups were replaced by a galactic translocation system that reduced consumption of PEP as intermediates [76].…”

Section: Primary Metabolitesmentioning

confidence: 99%

Primary metabolites from overproducing microbial system using sustainable substrates

Srivastava

Akhtar

Verma

et al. 2020

Biotech and App Biochem

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Primary (or secondary) metabolites are produced by animals, plants, or microbial cell systems either intracellularly or extracellularly. Production capabilities of microbial cell systems for many types of primary metabolites have been exploited at a commercial scale. But the high production cost of metabolites is a big challenge for most of the bioprocess industries and commercial production needs to be achieved. This issue can be solved to some extent by screening and developing the engineered microbial systems via reconstruction of the genome‐scale metabolic model. The predicted genetic modification is applied for an increased flux in biosynthesis pathways toward the desired product. Wherein the resulting microbial strain is capable of converting a large amount of carbon substrate to the expected product with minimum by‐product formation in the optimal operating conditions. Metabolic engineering efforts have also resulted in significant improvement of metabolite yields, depending on the nature of the products, microbial cell factory modification, and the types of substrate used. The objective of this review is to comprehend the state of art for the production of various primary metabolites by microbial strains system, focusing on the selection of efficient strain and genetic or pathway modifications, applied during strain engineering.

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Genetic manipulation of Escherichia coli central carbon metabolism for efficient production of fumaric acid

Cited by 27 publications

References 31 publications

Engineering the transmission efficiency of the noncyclic glyoxylate pathway for fumarate production in Escherichia coli

Engineering the transmission efficiency of the noncyclic glyoxylate pathway for fumarate production in Escherichia coli

Applications of one-Step environmentally-friendly fermentation method to produce fumaric acid with immobilized Rhizopus arrhizus in stirred-tank reactor

Primary metabolites from overproducing microbial system using sustainable substrates

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