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Metabolic engineering of Escherichia coli for the production of phenylalanine and related compounds

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Abstract

In this review, the metabolic engineering approaches including those used by the authors in creating phenylalanine producers based on Escherichia coli were systematized. Optimization of the amino acid biosynthesis was conducted in order to obtain significant quantities of phenylalanine and to ensure the availability of its direct precursors in cell metabolism—erythrose 4-phosphate and phosphoenolpyruvic acid. The possibility of altering global regulation mechanisms was investigated for a full reorientation of the metabolism to phenylalanine synthesis with the use of Csr (carbon storage regulator). The identification of the aromatic amino acids exporter YddG is associated with the use of the phenylalanine producer as a test-system. Novel approaches to phenylalanine producer construction (use of the “leaky” allele tyrA—ssrA, promoters of the phosphate regulon), as well as new methods of obtaining producers of similar amino acid tyrosine, were discussed. Examples of the synthesis of useful aromatic compounds from phenylalanine or its precursor, phenylpyruvic acid, with E. coli as the ecipient for foreign gene expression were examined.

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Abbreviations

CB:

culture broth

PCR:

polymerase chain reaction

ATP:

adenosine triphosphate

FBA:

flux balance analysis

CSR:

carbon storage regulator

DAHP-synthase:

3-Deoxy-D-arabinoheptulosonate 7-phosphate synthase

E-4-P:

erythrose 4-phosphate

MFA:

metabolic flux analysis

NADPH:

nicotinamide adenine dinucleotide phosphate

PEP:

phosphoenolpyruvate

Phe:

phenylalanine

Pi:

inorganic phosphate

PTS:

phosphotransferase system

Pyr:

pyruvate

TCA cycle:

tricarboxylic acid cycle.

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  1. Ajinomoto-Genetika Research Institute, Moscow, 117545, Russia

    V. G. Doroshenko, V. A. Livshits, L. G. Airich, I. S. Shmagina, E. A. Savrasova, M. V. Ovsienko & S. V. Mashko

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  1. V. G. Doroshenko
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  2. V. A. Livshits
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  3. L. G. Airich
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  4. I. S. Shmagina
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  5. E. A. Savrasova
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  6. M. V. Ovsienko
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  7. S. V. Mashko
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Original Russian Text © V.G. Doroshenko, V.A. Livshits, L.G. Airich, I.S. Shmagina, E.A. Savrasova, M.V. Ovsienko, S.V. Mashko, 2014, published in Biotekhnologiya, 2014, No. 4, pp. 8–27.

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Doroshenko, V.G., Livshits, V.A., Airich, L.G. et al. Metabolic engineering of Escherichia coli for the production of phenylalanine and related compounds. Appl Biochem Microbiol 51, 733–750 (2015). https://doi.org/10.1134/S0003683815070017

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