Lysine biosyntheis

Lysine biosynthesis is one of the unique metabolic capabilities of cyst forming Coccidia such as Toxoplasma gondii. Toxoplasma genome analysis shows that it has the unique metabolic capability to synthesise lysine, an essential amino acid in humans. This capability is absent in other Apicomplexa. Toxoplasma can convert aspartate into lysine via the diaminopimelate pathway [1]. This pathway takes place via four different routes in different organisms (KEGG Lysine biosynthesis pathway). Of these, three variants belong to different groups of prokaryotes and the plant variant of the pathway was identified recently in Arabidopsis thaliana [2]. The first four enzymes (aspartate kinase, aspartate semialdehyde dehydrogenase, dihydrodipicolinate synthase and dihydrodipicolinate reductase) and the last enzyme (diaminopimelate decarboxylase) is the same in all variants of the pathway and these five enzymes are present in Toxoplasma.  Of these five enzymes, diaminopimelate decarboxylase, the last enzyme of the pathway is the only protein to have peptide evidence from MS-based proteomics so far. The homology-based analysis of the Toxoplasma genome has not led to identification of the middle enzymes of any routes even with low sequence similarity. The reason for this is unknown which could be absence of the functional pathway, errors in gene models or the pathway may take place via another route in Toxoplasma and the enzymes involved may be present as hypothetical proteins in the genome.

 

Enzyme EC Number Gene id Protein localisation Localisation data source
Aspartate semialdehyde dehydrogenase 1.2.1.11 TGME49_205420 Cytosol GO annotation
4-hydroxy-tetrahydrodipicolinate reductase 1.17.1.8 TGME49_243680 Cytosol GO annotation
Aspartate kinase 2.7.2.4 TGME49_227090    
Diaminopimelate decarboxylase 4.1.1.20 TGME49_278740    
4-hydroxy-tetrahydrodipicolinate synthase 4.3.3.7 TGME49_242300    

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
L-Aspartate Asparagine and aspartate metabolism, Host Lysine Lysine degradation
Pyruvate Glycolysis