Team:UNAM Genomics/Project/Overview

Overview

Tetrahydrobiopterin is an essential cofactor for the aromatic amino acid hydroxylases and also essential for the synthesis of nitric oxide by nitric oxide synthase. This cofactor is used for the treatment for certain types of phenylketonuria. However the current obtaining of this cofactor is through chemical synthesis, in a process that is very expensive causing a 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, a cofactor for some aromatic aminoacid hydroxylases, i. e. phenylalanine hydroxylase. 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 regulation in order to achieve a better production while considering biosafety and doing a biosensor