l-threonine production by l-aspartate- and l-homoserine-resistant mutant of Escherichia coli

Furukawa, Shigetada; Ozaki, Akio; Nakanishi, Toshihide

doi:10.1007/bf00260983

Cited by 12 publications

(4 citation statements)

References 6 publications

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“…In E. coli, threonine production was increased to 76 g l -1 by conventional mutagenesis and selection/screening techniques. Of major importance were mutations to decrease regulation of the pathway and of degradation of the amino acid (Furukawa et al, 1988). Recently, a comparative analyses of transcriptome, proteome and nucleotide sequences between a prototrophic (W3110) and an L-threonine-producing E. coli TF5015 was carried out (Lee et al, 2003).…”

Section: L-threoninementioning

confidence: 99%

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Metabolic regulation and overproduction of primary metabolites

Sánchez

Demain

2008

Microbial Biotechnology

146

103

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SummaryOverproduction of microbial metabolites is related to developmental phases of microorganisms. Inducers, effectors, inhibitors and various signal molecules play a role in different types of overproduction. Biosynthesis of enzymes catalysing metabolic reactions in microbial cells is controlled by well‐known positive and negative mechanisms, e.g. induction, nutritional regulation (carbon or nitrogen source regulation), feedback regulation, etc. The microbial production of primary metabolites contributes significantly to the quality of life. Fermentative production of these compounds is still an important goal of modern biotechnology. Through fermentation, microorganisms growing on inexpensive carbon and nitrogen sources produce valuable products such as amino acids, nucleotides, organic acids and vitamins which can be added to food to enhance its flavour, or increase its nutritive values. The contribution of microorganisms goes well beyond the food and health industries with the renewed interest in solvent fermentations. Microorganisms have the potential to provide many petroleum‐derived products as well as the ethanol necessary for liquid fuel. Additional applications of primary metabolites lie in their impact as precursors of many pharmaceutical compounds. The roles of primary metabolites and the microbes which produce them will certainly increase in importance as time goes on. In the early years of fermentation processes, development of producing strains initially depended on classical strain breeding involving repeated random mutations, each followed by screening or selection. More recently, methods of molecular genetics have been used for the overproduction of primary metabolic products. The development of modern tools of molecular biology enabled more rational approaches for strain improvement. Techniques of transcriptome, proteome and metabolome analysis, as well as metabolic flux analysis. have recently been introduced in order to identify new and important target genes and to quantify metabolic activities necessary for further strain improvement.

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Section: L-threoninementioning

confidence: 99%

“…In E. coli , threonine production was increased to 76 g l −1 by conventional mutagenesis and selection/screening techniques. Of major importance were mutations to decrease regulation of the pathway and of degradation of the amino acid ( Furukawa et al. , 1988 ).…”

Section: Microbial Processesmentioning

confidence: 99%

Metabolic regulation and overproduction of primary metabolites

Sánchez

Demain

2008

Microbial Biotechnology

146

103

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“…In microorganisms and plants, l ‐threonine can be generated from l ‐aspartate, and the enzymes in the synthetic pathway consist of aspartokinase, β‐aspartate semialdehyde dehydrogenase, homoserine dehydrogenase, homoserine kinase, and threonine synthase (Dong, Quinn, & Wang, ). In industry, l ‐threonine is primarily produced by fermentation of microbes, such as Escherichia coli (Furukawa, Ozaki, & Nakanishi, ), Serratia marcescens (Komatsubara, Kisumi, Murata, & Chibata, ), and Corynebacterium glutamicum (Palmieri, Berns, Krämer, & Eikmanns, ). Currently, E. coli strain, attained by traditional screening and random mutagenesis, remains the dominant l ‐threonine producer (Dong et al, ).…”

Section: Introductionmentioning

confidence: 99%

Two‐stage carbon distribution and cofactor generation for improving l‐threonine production of Escherichia coli

Liu

Xiong

et al. 2018

Biotech & Bioengineering

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L-Threonine, a kind of essential amino acid, has numerous applications in food, pharmaceutical, and aquaculture industries. Fermentative L-threonine production from glucose has been achieved in Escherichia coli. However, there are still several limiting factors hindering further improvement of L-threonine productivity, such as the conflict between cell growth and production, byproduct accumulation, and insufficient availability of cofactors (adenosine triphosphate, NADH, and NADPH).Here, a metabolic modification strategy of two-stage carbon distribution and cofactor generation was proposed to address the above challenges in E. coli THRD, an L-threonine producing strain. The glycolytic fluxes towards tricarboxylic acid cycle were increased in growth stage through heterologous expression of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, and citrate synthase, leading to improved glucose utilization and growth performance. In the production stage, the carbon flux was redirected into L-threonine synthetic pathway via a synthetic genetic circuit. Meanwhile, to sustain the transaminase reaction for L-threonine production, we developed an L-glutamate and NADPH generation system through overexpression of glutamate dehydrogenase, formate dehydrogenase, and pyridine nucleotide transhydrogenase. This strategy not only exhibited 2.02-and 1.21-fold increase in L-threonine production in shake flask and bioreactor fermentation, respectively, but had potential to be applied in the production of many other desired oxaloacetate derivatives, especially those involving cofactor reactions. K E Y W O R D Scarbon distribution, cofactor generation, Escherichia coli, L-threonine, metabolic engineering

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“…87 In E. coli, introduction of a high-copy number-plasmid with a mutated threonine operon led to overproduction. 94 E. coli dominates the commercial threonine fermentation owing to their dynamic growth pattern and better substrate utilization, but the chances of endotoxin production make them inapplicable in the synthesis of pharmaceutical and food grade amino acid. The genes coding for the enzymes that consume threonine for isoleucine and glycine synthesis were mutated to attain threonine overproduction.…”

Section: Threoninementioning

confidence: 99%