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Literature summary for 1.1.1.3 extracted from

  • Liu, P.; Zhang, B.; Yao, Z.H.; Liu, Z.Q.; Zheng, Y.G.
    Multiplex design of the metabolic network for production of L-homoserine in Escherichia coli (2020), Appl. Environ. Microbiol., 86, e01477-20 .
    View publication on PubMed
Search for more literature for 1.1.1.3

Cloned(Commentary)

Cloned (Comment) Organism
gene thrA, recombinant overexpression of enzyme mutant G433R in Escherichia coli strain Bl21 Escherichia coli

Protein Variants

Protein Variants Comment Organism
G433R site-directed mutagenesis, strain HS33/pACYC-pycP458S-thrAG433R-lysC shows increased activity (62.4% of the maximum theoretical yield) Escherichia coli
additional information key metabolic pathway for construction of an inducer-free L-homoserine-producing strain to maximize the productivity of L-homoserine based on genetic-engineering tools, comparison of L-homoserine production, cell growth, and glucose consumption in different engineered strains, overview. L-Homoserine is a nonessential amino acid for the biosynthesis of L-threonine and L-methionine. It is also an important precursor for the production of isobutanol, 1,4-butanediol, L-phosphinothricin, 2,4-ihydroxybutyrate, and 1,3-propanediol. The initial L-homoserine-producing strain HS1 is obtained by blocking the degradative and competitive pathways and overexpressing thrA (encoding homoserine dehydrogenase) based on an O-succinyl homoserine-producing strain, using the pull-push-block strategy, an efficient method to engineer microorganisms involved in biosynthesizing target products by modifying metabolic networks. L-homoserine-converting pathway-related genes (thrB, encoding homoserine kinase, and metA, encoding homoserine O-succinyltransferase) are successively deleted to block L-homoserine degradation. Gene thrA is overexpressed to push the carbon flux to L-homoserine production. Then, the lysine-auxotrophic strain HS2 is generated by deleting lysA to eliminate a precursor competing metabolic pathway on L-homoserine production. For strengthening the capability of the L-homoserine transport system and the transformation of other toxic intermediate metabolites, gene rhtA, encoding the inner membrane transporter that is involved in the export of L-homoserine, is overexpressed chromosomally by replacing the native promoter with the trc promoter to obtain strain HS3 (Trc-rhtA). The strain shows increased activity. Increase in the L-homoserine export capacity and relieve the growth burden of homoserine-producing strains to enable survival via replacement of the native promoter of the eamA gene by the trc promoter in strain HS4 (Trc-eamA). Two rhtA gene copies (the native rhtA gene and replacement of the lacI gene) and eamA are overexpressed under the trc promoter in the chromosome to construct strain HS5 (DELTAlacI::Trc-rhtA Trc-rhtA Trc-eamA). Under batch culture, strain HS5, with modification of the transport system and construction of a constitutive expression system, can produce 3.14 g/l L-homoserine, which is 54.2% higher than strain HS2 production. In addition, the specific production of strain HS5 is also increased. Repression of candidate genes by the CRISPRi system to further enhance L-homoserine production Escherichia coli
P458S site-directed mutagenesis, strain HS33/pACYC-pycP458S-thrAG433R-lysC shows increased activity (62.4% of the maximum theoretical yield) Escherichia coli

Inhibitors

Inhibitors Comment Organism Structure
additional information L-homoserine inhibits the activity of aspartokinase encoded by metL Escherichia coli

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
L-homoserine + NAD+ Escherichia coli
-
 L-aspartate 4-semialdehyde + NADH + H+
-
 ?
L-homoserine + NAD+ Escherichia coli W3110
-
 L-aspartate 4-semialdehyde + NADH + H+
-
 ?

Organism

Organism UniProt Comment Textmining
Escherichia coli P00561
-
-
Escherichia coli W3110 P00561
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-homoserine + NAD+
-
 Escherichia coli L-aspartate 4-semialdehyde + NADH + H+
-
 ?
L-homoserine + NAD+
-
 Escherichia coli W3110 L-aspartate 4-semialdehyde + NADH + H+
-
 ?
additional information the bifunctional enzyme also exhibits aspartokinase activity, EC 2.7.2.4 Escherichia coli ?
-
-
additional information the bifunctional enzyme also exhibits aspartokinase activity, EC 2.7.2.4 Escherichia coli W3110 ?
-
-

Synonyms

Synonyms Comment Organism
More see also EC 2.7.2.4 Escherichia coli
thrA
-
 Escherichia coli

Cofactor

Cofactor Comment Organism Structure
NAD+
-
 Escherichia coli
NADH
-
 Escherichia coli