Combined metabolic analyses for the biosynthesis pathway of l-threonine in Escherichia coli

Yang, Qiang; Cai, Dongbo; Chen, Wenshou; Wei, Luo

doi:10.3389/fbioe.2022.1010931

Cited by 5 publications

(4 citation statements)

References 33 publications

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“…In this study, a wild strain producing l -threonine, E. coli TWF001, was selected as the starting strain. Since the strong promoter P trc would be used in subsequent experiments, the lacI gene on the TWF001 chromosome was first knocked out, resulting in TWF001Δ lacI .…”

Section: Resultsmentioning

confidence: 99%

“…Obviously, the L-threonine catabolism pathway triggered by threonine dehydrogenase is a key determinant in the synthesis of 2,5- DMP. In this study, a wild strain producing L-threonine, E. coli TWF001, 20 was selected as the starting strain. Since the strong promoter P trc would be used in subsequent experiments, the lacI gene on the TWF001 chromosome was first knocked out, resulting in TWF001ΔlacI.…”

Section: Reconstructing the 25-dmp Biosynthetic Pathwaymentioning

confidence: 99%

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Metabolic Engineering of Escherichia coli for Production of 2,5-Dimethylpyrazine

Zeng,

Wu,

Han

et al. 2024

J. Agric. Food Chem.

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2,5-Dimethylpyrazine (2,5-DMP) is a high-value-added alkylpyrazine compound with important applications in both the food and pharmaceutical fields. In response to the increasing consumer preference for natural products over chemically synthesized ones, efforts have been made to develop efficient microbial cell factories for the production of 2,5-DMP. However, the previously reported recombinant strains have exhibited low yields and relied on expensive antibiotics and inducers. In this study, we employed metabolic engineering strategies to develop an Escherichia coli strain capable of producing 2,5-DMP at high levels without the need for inducers or antibiotics. Initially, the biosynthesis pathway of 2,5-DMP was constructed that realized 2,5-DMP production from glucose. Subsequently, efforts focused on enhancing 2,5-DMP production by improving the availability of the cofactor NAD + and precursor L-threonine. Additionally, the supply and conversion of L-threonine were balanced by optimizing the copy number of the key gene tdh on the chromosome and by modifying the L-threonine transport system. The final engineering strain D19 produced 3.1 g/L of 2,5-DMP, which is the highest titer for fermentative production of 2,5-DMP using glucose as the carbon source up to date. The strategies used in this study lay a good foundation for the production of 2,5-DMP on a large scale.

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Section: Resultsmentioning

confidence: 99%

Section: Reconstructing the 25-dmp Biosynthetic Pathwaymentioning

confidence: 99%

Metabolic Engineering of Escherichia coli for Production of 2,5-Dimethylpyrazine

Zeng,

Wu,

Han

et al. 2024

J. Agric. Food Chem.

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“…When the fermentation temperature was set at 37 °C at first 6 h and then shifted to 42 °C, the resulting strain TWF113/pFT24rpa1 produced L-Thr at a yield of 124.03% mol/mol, which exceeds the maximum available theoretical value (122.47%) [ 81 ]. In other metabolic regulation strategies, Yang et al added L-glutamic acid into a medium for migrating the metabolic flow to L-Thr, resulting in a titer of 77 g/L by fed-batch fermentation, 10% higher than that without the addition of L-glutamic acid [ 205 ].…”

Section: L-threoninementioning

confidence: 99%

Recent Advances in Metabolic Engineering for the Biosynthesis of Phosphoenol Pyruvate–Oxaloacetate–Pyruvate-Derived Amino Acids

Yin,

Zhou,

Ding

et al. 2024

Molecules

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The phosphoenol pyruvate–oxaloacetate–pyruvate-derived amino acids (POP-AAs) comprise native intermediates in cellular metabolism, within which the phosphoenol pyruvate–oxaloacetate–pyruvate (POP) node is the switch point among the major metabolic pathways existing in most living organisms. POP-AAs have widespread applications in the nutrition, food, and pharmaceutical industries. These amino acids have been predominantly produced in Escherichia coli and Corynebacterium glutamicum through microbial fermentation. With the rapid increase in market requirements, along with the global food shortage situation, the industrial production capacity of these two bacteria has encountered two bottlenecks: low product conversion efficiency and high cost of raw materials. Aiming to push forward the update and upgrade of engineered strains with higher yield and productivity, this paper presents a comprehensive summarization of the fundamental strategy of metabolic engineering techniques around phosphoenol pyruvate–oxaloacetate–pyruvate node for POP-AA production, including L-tryptophan, L-tyrosine, L-phenylalanine, L-valine, L-lysine, L-threonine, and L-isoleucine. Novel heterologous routes and regulation methods regarding the carbon flux redistribution in the POP node and the formation of amino acids should be taken into consideration to improve POP-AA production to approach maximum theoretical values. Furthermore, an outlook for future strategies of low-cost feedstock and energy utilization for developing amino acid overproducers is proposed.

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“…In the past decades, improvements in l -threonine fermentation technology have allowed l -threonine to be used as an abundant and affordable potential bulk stock for biobased production. − l -threonine has been widely used as a substrate for preparing various industrial products, such as α-ketobutyric acid, d -lactate, and l -2-aminobutyric acid. − In addition, l -threonine is not toxic and can be efficiently utilized by Escherichia coli . Thus, the production of acetyl-CoA-derived compounds from l -threonine is economically viable if the yield of target compounds from l -threonine is high.…”

Section: Introductionmentioning

confidence: 99%

Engineering a Novel Acetyl-CoA Pathway for Efficient Biosynthesis of Acetyl-CoA-Derived Compounds

Nie,

Wang,

Zhang

2023

ACS Synth. Biol.

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Acetyl-CoA is an essential central metabolite in living organisms and a key precursor for various value-added products as well. However, the intracellular availability of acetyl-CoA limits the efficient production of these target products due to complex and strict regulation. Here, we proposed a new acetyl-CoA pathway, relying on two enzymes, threonine aldolase and acetaldehyde dehydrogenase (acetylating), which can convert one L-threonine into one acetyl-CoA, one glycine, and generate one NADH, without carbon loss. Introducing the acetyl-CoA pathway could increase the intracellular concentration of acetyl-CoA by 8.6-fold compared with the wild-type strain. To develop a cost-competitive and genetically stable acetyl-CoA platform strain, the new acetyl-CoA pathway, driven by the constitutive strong promoter, was integrated into the chromosome of Escherichia coli. We demonstrated the practical application of this new acetyl-CoA pathway by high titer production of β-alanine, mevalonate, and N-acetylglucosamine. At the same time, this pathway achieved a high-yield production of glycine, a value-added commodity chemical for the synthesis of glyphosate and thiamphenicol. This work shows the potential of this new acetyl-CoA pathway for the industrial production of acetyl-CoA-derived compounds.

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Combined metabolic analyses for the biosynthesis pathway of l-threonine in Escherichia coli

Cited by 5 publications

References 33 publications

Metabolic Engineering of Escherichia coli for Production of 2,5-Dimethylpyrazine

Metabolic Engineering of Escherichia coli for Production of 2,5-Dimethylpyrazine

Recent Advances in Metabolic Engineering for the Biosynthesis of Phosphoenol Pyruvate–Oxaloacetate–Pyruvate-Derived Amino Acids

Engineering a Novel Acetyl-CoA Pathway for Efficient Biosynthesis of Acetyl-CoA-Derived Compounds

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