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Directed modification of Escherichia coli metabolism for the design of threonine-producing strains

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Abstract

The modification of Escherichia coli K-12 metabolism leading to threonine overproduction is the most studied system in synthetic biology that has been used to elaborate the majority of the currently known approaches to constructing microbial producers. They include optimization of biosynthesis through search for rate-limiting stages, modification of substrate and product transport, elimination of side metabolic pathways and degradation systems, reinforcement of the regeneration of coenzymes that are required for product biosynthesis, and exclusion of futile cycles and metabolic pathways with low energy efficiency. Extensive research in functional genomics made it possible to selectively remove the “unnecessary genes,” the functions of which are useless for producing a strain or adversely affect its properties. In total, using various approaches to designing threonine-producing strains, over 150 genome loci that affect more than 30% genes in E. coli were directly modified, thus providing interesting data for researchers in the field of microbial synthesis, as well as in related biological sciences. This review is dedicated to the assessment of genetic engineering modifications in E. coli metabolism (primarily, on the basis of modern patent literature) that ensure threonine overproduction.

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Abbreviations

CA1-GD1:

aspartokinase I-homoserine dehydrogenase I

AKIII:

aspartokinase III

acetyl-CoA:

acetyl coenzyme A

VKPM:

All-Russian Collection of Industrial Microorganisms

PA:

pyruvic acid

PEP:

phosphoenolpyruvate

PTS:

phosphotransferase system

TAC:

tricarboxylic acid cycle

OAA:

oxaloacetic acid

ADM:

Archer Daniels Midland Co. (United States)

ATCC:

American-Type Culture Collection (United States)

CJ:

Cheil Jedang Co. (South Korea)

FERM:

Fermentation Research Institute, Agency of Industrial Science and Technology (Japan)

IS:

insertion sequence

KCCM:

Korean Culture Center of Microorganisms (South Korea)

KFCC:

Korean Federation of Culture Collections (South Korea)

NRRL:

Agricultural Research Service Culture Collection (United States)

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  1. State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow, 117545, Russia

    T. V. Yuzbashev, T. V. Vybornaya, A. S. Larina, I. T. Gvilava, N. E. Voyushina, S. S. Mokrova, E. Yu. Yuzbasheva, I. V. Manukhov, S. P. Sineoky & V. G. Debabov

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  1. T. V. Yuzbashev
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Original Russian Text © T.V. Yuzbashev, T.V. Vybornaya, A.S. Larina, I.T. Gvilava, N.E. Voyushina, S.S. Mokrova, E.Yu. Yuzbasheva, I.V. Manukhov, S.P. Sineoky, V.G. Debabov, 2013, published in Biotekhnologiya, 2013, No. 2, pp. 8–33.

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Yuzbashev, T.V., Vybornaya, T.V., Larina, A.S. et al. Directed modification of Escherichia coli metabolism for the design of threonine-producing strains. Appl Biochem Microbiol 49, 723–742 (2013). https://doi.org/10.1134/S0003683813090056

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