Difference between revisions of "Part:BBa K4140025"

Revision as of 10:05, 8 October 2022

PAH releasing device

Part Description

Coding sequence for an enzyme that causes phenylalanine to be hydroxylated in order to produce tyrosine. PAH is a hydroxylase that needs biopterin. It's linked to KP-SP ISA secreting peptide signal at the N-terminus of the protein to transmit it from intra cellular to extra cellula

Usage

We are developing a tunable therapeutic approach to give the body the ability to produce phenylalanine hydroxylase (PAH) by implementing our designed therapeutic circuit in a cell-based system that produces PAH according to phenylalanine and tyrosine levels as shown in figure 1. In the presence of phenylalanine (Phe), the TyrR will activate tyrP, accordingly tyrP will enhance the production of PAH gene. While the inhibitory effect of the ParoF will not be initiated, thus L7Ae will be expressed, preventing the expression of the dcas12g.

Figure 1. (shows the E.coli-based system in our therapeutic platform.)

Characterization by mathematical modeling

We are using mathematical modeling to detect the increased level of phenylalanine (phe) in phenylketonuria patients in our therapeutic platform. It depends on a whole cell-based biosensor through a cascade of reactions to finally end by formation of PAH that is deficient in PKU patients as shown in graph (1).

Graph(1) illustrates a direct relation between phenylalanine and PAH ,so as the biomarker increases, the released amount of the enzyme increases till it reaches constant value after about 30 time units. Therefore, the maximum amount of the biomarker releases the maximum amount of PAH. Sequence and Features