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Revision as of 03:56, 16 August 2014
Overview
Tetrahydrobiopterin (BH4) is an essential cofactor for some aromatic amino acid hydroxylases, i. e. phenylalanine hydroxylase. Also, it is essential for the synthesis of nitric oxide by nitric oxide synthase. BH4 is used for the treatment for certain types of phenylketonuria. However, the current large-scale source of this cofactor is through chemical synthesis, a very expensive process, reflected in the considerable rise on the medicine's price.
Previously, Yamamoto, et al. [1] reported a construction with the three genes involved in the biosynthesis of tetrahydrobiopterin. The genes were in a low copy number plasmid and organized as three transcriptional units under the control of the lac promoter. However, there was a problem: if the first enzyme of the pathway (GTP cyclohydrolase I) was overexpressed, the BH4 yield was reduced because of the formation of inclusion bodies. So, we propose to change gene regulation in order to achieve a better production while considering biosafety and creating a biosensor.
- 1-Yamamoto, K., Kataoka, E., Miyamoto, N., Furukawa, K., Ohsuye, K., & Yabuta, M. (2003). Genetic engineering of E scherichia coli for production of tetrahydrobiopterin. Metabolic Engineering, 5(4), 246-254.
