Recombinant Salmonella typhimurium Aromatic-amino-acid aminotransferase (tyrB)

Overview of Recombinant Salmonella typhimurium Aromatic-Amino-Acid Aminotransferase (tyrB)

Recombinant Salmonella typhimurium aromatic-amino-acid aminotransferase (tyrB) refers to engineered forms of the enzyme encoded by the tyrB gene, which catalyzes transamination reactions involving aromatic amino acids (tyrosine, phenylalanine, and tryptophan). This enzyme is critical for amino acid metabolism, enabling the interconversion of aromatic amino acids and α-keto acids. Structural and functional studies highlight its homology to Escherichia coli aromatic aminotransferase (ArAT), with 87.9% sequence identity .

Table 1: Comparative Sequence and Functional Data

Functional Complementation in E. coli

When expressed in E. coli mutants lacking intrinsic tyrB, the S. typhimurium tyrB gene restores transamination activity for tyrosine and phenylalanine, confirming its conserved enzymatic role .

Role in Methionine Biosynthesis

In Klebsiella pneumoniae, a homologous TyrAT (83% identity to S. typhimurium tyrB) catalyzes the final step of methionine regeneration via transamination of α-keto-methiobutyrate . This suggests potential metabolic overlap in S. typhimurium.

Recombinant Vaccine Platforms

Recombinant Salmonella strains, such as YS1646, integrate heterologous antigens (e.g., Schistosoma Cathepsin B) via chromosomal insertion. While tyrB is not directly implicated in antigen expression, its role in host amino acid metabolism may influence bacterial persistence and immunogenicity .

Phylogenetic Diversity

Genomic analyses of S. typhimurium reveal strain-specific variations in tyrB and related metabolic genes. For example, ST34 (monophasic S. 4,,12:i:-) exhibits reduced genomic diversity compared to S. typhimurium, though tyrB remains conserved .

Impact of aroA Deletion

Deletion of aroA (a shikimate pathway gene) in S. typhimurium increases immunogenicity and virulence. While tyrB is not directly targeted, disruptions in aromatic amino acid biosynthesis may alter metabolic fluxes, indirectly affecting tyrB activity .

Cancer Therapy

Attenuated S. typhimurium strains with aroA or lipid A modifications show enhanced tumor colonization. Though tyrB’s role is indirect, its involvement in amino acid metabolism could optimize bacterial growth in nutrient-limited tumor microenvironments .

Enzyme Engineering

Mutagenesis studies in E. coli tyrB (e.g., V39L/K41Y/T47I/N69L/T109S) demonstrate potential to broaden substrate specificity. Similar approaches in S. typhimurium tyrB could enhance biocatalytic applications .

Future Directions

1. Structural Studies: Crystallographic analysis to elucidate S. typhimurium tyrB’s active-site conformation and substrate binding.

2. Synthetic Biology: Engineering tyrB for optimized transamination in biofuel or pharmaceutical production.

3. Host-Pathogen Interactions: Investigating tyrB’s role in S. typhimurium persistence and immune evasion.