Metabolic pathways and fermentative production of <scp>L</scp>‐aspartate family amino acids

Park, Jin Hwan; Lee, Sang Yup

doi:10.1002/biot.201000032

Cited by 83 publications

(49 citation statements)

References 105 publications

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“…For decades, the development of industrial host strains for L-threonine production has relied on the traditional metabolic engineering and systems biology approach, which focused on increases in metabolic flux through the L-threonine biosynthetic pathway by deleting the competing pathways, elimination of feedback inhibition in the biosynthetic pathway, amplification of the rate-limiting enzyme, and export of the L-threonine produced (1,3,4,9,11,30,(45)(46)(47)(48)(49). The engineered host strains were able to produce L-threonine with a high yield close to a theoretical maximum (8,50).…”

Section: Discussionmentioning

confidence: 99%

“…These studies allow a novel approach of assembling only beneficial genetic modifications in a production host to be taken. This genomics-based strain construction is now being carried out successfully (8)(9)(10)(11).Despite all these efforts, strain improvements are still hampered by intrinsic drawbacks of metabolic reactions. The actual metabolic reactions of amino acid biosynthetic pathways in microorganisms are mediated by simple diffusion and random collisions of metabolites and enzymes, which cause metabolic reactions to be inefficient by lowering the local metabolite concentration around the enzymes (12).…”

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confidence: 99%

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confidence: 99%

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Improved Production of l -Threonine in Escherichia coli by Use of a DNA Scaffold System

Lee

Jung

Bui

et al. 2013

Appl Environ Microbiol

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Despite numerous approaches for the development of L-threonine-producing strains, strain development is still hampered by the intrinsic inefficiency of metabolic reactions caused by simple diffusion and random collisions of enzymes and metabolites. A scaffold system, which can promote the proximity of metabolic enzymes and increase the local concentration of intermediates, was reported to be one of the most promising solutions. Here, we report an improvement in L-threonine production in Escherichia coli using a DNA scaffold system, in which a zinc finger protein serves as an adapter for the site-specific binding of each enzyme involved in L-threonine production to a precisely ordered location on a DNA double helix to increase the proximity of enzymes and the local concentration of metabolites to maximize production. The optimized DNA scaffold system for L-threonine production significantly increased the efficiency of the threonine biosynthetic pathway in E. coli, substantially reducing the production time for L-threonine (by over 50%). In addition, this DNA scaffold system enhanced the growth rate of the host strain by reducing the intracellular concentration of toxic intermediates, such as homoserine. Our DNA scaffold system can be used as a platform technology for the construction and optimization of artificial metabolic pathways as well as for the production of many useful biomaterials.A s the building blocks of life, amino acids have long played an important role in both human and animal nutrition and health maintenance. On account of its functionality and the special features arising from chirality, this class of compounds is extremely important and of great interest for the chemical industry (1). Of the 20 standard amino acids, the 9 essential amino acids (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine) occupy a key position, in that they are not synthesized in animals and humans but must be ingested with feed or food (2).Production methods for these essential amino acids are broadly classified into three types: extraction, chemical synthesis, and microbial fermentation. Among these methods, the microbial fermentation method is being widely applied to the industrial production of most essential amino acids, except for a few kinds of L-amino acids for which high production yields have not been achieved by fermentation (1). The advances in the industrial production of amino acids are closely connected with screening or selection of suitable putative production hosts and subsequent improvement of production strains. Previous attempts at strain improvement have relied on classical mutagenesis and screening procedures, which focused on deleting competing pathways and eliminating feedback regulations in the biosynthetic pathway (1, 3-7). The recent trend of whole-genome analysis and systems biology has begun to exert a profound effect on the strategy of strain development. The barrage of information has led to a better understanding of the architecture of cel...

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Section: Discussionmentioning

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Improved Production of l -Threonine in Escherichia coli by Use of a DNA Scaffold System

Lee

Jung

Bui

et al. 2013

Appl Environ Microbiol

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“…glutamicum is reported to be a commonly used microorganism in industrial L-isoleucine production and genetic engineering has improve L-isoleucine yield (Park and Lee, 2010;Yin et al, 2012;Wang et al, 2013). Model iJM658 simulated three additional promising gene knockout strategies identified by a single-gene deletion method (Table 3).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Reconstruction and analysis of a genome-scale metabolic network of Corynebacterium glutamicum S9114

Mei

et al. 2016

Gene

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“…E. coli also contains high aspartase and aspartate transaminase activities at levels comparable to those of fumarase and malate dehydrogenase [14]. These two enzymatic activities form an alternative pathway for the formation of fumarate and serve as the initial step for the synthesis of several important amino acids [46].…”

Section: Anaerobic Metabolic Pathways To C4 Diacidsmentioning

confidence: 99%

Metabolically engineered Escherichia coli for biotechnological production of four-carbon 1,4-dicarboxylic acids

Cao

Lin

2010

J Ind Microbiol Biotechnol

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Confronted with inescapable exhaustion of the earth's fossil energy resources, the bio-based process to produce industrial chemicals is receiving significant interest. Biotechnological production of four-carbon 1,4-dicarboxylic acids (C4 diacids) from renewable plant biomass is a promising and attractive alternative to conventional chemistry routes. Although the C4 diacids pathway is well characterized and microorganisms able to convert biomass to these acids have been isolated and described, much still has to be done to make this process economically feasible. Metabolically engineered Escherichia coli has been developed as a biocatalyst to provide new processes for the biosynthesis of many valuable chemicals. However, E. coli does not naturally produce C4 diacids in large quantities. Rational strain development by metabolic engineering based on efficient genetic tools and detailed knowledge of metabolic pathways are crucial to successful production of these compounds. This review summarizes recent efforts and experiences devoted to metabolic engineering of the industrial model bacteria E. coli that led to efficient recombinant biocatalysts for the production of C4 diacids, including succinate, fumarate, malate, oxaloacetate, and aspartate, as well as the key limitations and challenges. Continued advancements in metabolic engineering will help to improve the titers, yields, and productivities of the C4 diacids discussed here.

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Metabolic pathways and fermentative production of L‐aspartate family amino acids

Cited by 83 publications

References 105 publications

Improved Production of l -Threonine in Escherichia coli by Use of a DNA Scaffold System

Improved Production of l -Threonine in Escherichia coli by Use of a DNA Scaffold System

Reconstruction and analysis of a genome-scale metabolic network of Corynebacterium glutamicum S9114

Metabolically engineered Escherichia coli for biotechnological production of four-carbon 1,4-dicarboxylic acids

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