L-Histidine: Biosynthesis and Benefits

Biosynthesis of L-Histidine

L-Histidine is an essential protein amino acid in food and has a wide range of applications in medicine. A recombinant strain of Corynebacterium glutamicum for efficient biosynthesis of l-histidine has been reported. To alleviate the feedback inhibition of l-histidine in this study, they constructed an ATP phosphoribosyltransferase mutant HisGT235P-Y56M based on molecular docking and high-throughput screening, which accumulated 0.83 g/L of l-histidine.

They then overexpressed rate-limiting enzymes (including HisGT235P-Y56M and PRPP synthetase) and knocked out the pgi gene in the competitive pathway, thereby increasing l-histidine production to 1.21 g/L. Additionally, the energy state was optimised by decreasing the level of reactive oxygen species and increasing adenosine triphosphate supply, resulting in titres up to 3.10 g/L in shake flasks. The final recombinant strain produced 5.07 g/L of histidine in a 3-litre bioreactor without the addition of antibiotics and chemical inducers.

Benefits of L-Histidine

L-Histidine is an essential amino acid with many human health benefits for growth, protection of nerve cells, repair of damaged tissues and production of blood cells and histamine.

Anti-inflammatory

Studies have shown that L-Histidine interacts with the metabolism of non-esterified fatty acids (NEFA). L-Histidine counteracts NEFA-induced inflammation in BMECs by inhibiting Gab2 expression.

Protecting the heart

An observational study of more than 1,100 African-Americans has shown that mutations leading to elevated levels of histidine are associated with a lower incidence of coronary heart disease. Treating damaged rat hearts (due to the blood supply restored after a heart attack stroke) with histidine showed better recovery. It is hypothesised that histidine reduces reactive oxidants and helps conserve energy (ATP).

Prevention of diabetes and stroke

In a study of 100 female researchers with obesity and metabolic syndrome, supplementation with L-histidine for 12 weeks resulted in reductions in insulin resistance (cells not responding to insulin as they should) and adiposity, as well as suppression of inflammation and oxidative stress.

Toxicity reduction

Studies showing the interaction of l-histidine bound ZnO and E. coli showed that as the concentration of l-histidine increased, the reactive oxygen species produced during the interaction of zinc oxide with E. coli with the addition of l-histidine was reduced, suggesting a decrease in the toxicity of zinc oxide.

References:

[1] MENG CHAI, LONG LIU*; Combinatorial Protein Engineering and Metabolic Engineering for Efficient Synthesis of l-Histidine in Corynebacterium glutamicum[J]. ACS Synthetic Biology, 2023. DOI:10.1021/acssynbio.3c00026.

[2] MENGZE LI . L-Histidine attenuates NEFA-induced inflammatory responses by suppressing Gab2 expression[J]. Life sciences, 2024. DOI:10.1016/j.lfs.2024.122672.

[3] SHRADDHA MAHAKAL, SANDESH R. JADKAR* Modification in Toxicity of l-Histidine-Incorporated ZnO Nanoparticles toward Escherichia coli[J]. ACS Omega, 2023. DOI:10.1021/acsomega.3c01183.

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