Part:BBa_K4414006

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TYR

Usage and Biology

Tyrosinase（TYR） is a key enzyme in melanin synthesis that catalyzes the rate-limiting step of the reaction. By activating tyrosine kinase can increase the yield of melanin, forming melanin deposition . The melanogenesis process is initiated with the oxidation of L-tyrosine to dopaquinone (DQ) by TYR. The resulting quinone will serve as a substrate for the synthesis of eumelanin and pheomelanin(Hearing & Jiménez, 1987). The formation of DQ is a rate-limiting step in the melanin synthesis because remainder of the reaction sequence can proceed spontaneously at a physiological pH value(Halaban et al., 2002). After DQ formation, it undergoes intramolecular cyclization to produce indoline, leukodopachrome (cyclodopa). The redox exchange between leukodopachrome and DQ give rise to dopachrome and L-3,4-dihydroxyphenylalanine (L-DOPA), which is also a substrate for TYR and oxidized to DQ again by the enzyme. Dopachrome gradually decomposes to give dihydroxyindole (DHI) and dihydroxyindole-2-carboxylicacid (DHICA). The later process is catalyzed by TRP-2, now known as dopachrome tautomerase (DCT). Ultimately, these dihydroxyindoles (DHI and DHICA) are oxidized to eumelanin. TRP-1 is believed to catalyze the oxidation of DHICA to eumelanin. Alongside, DQ is converted to 5-S-cysteinyldopa or glutothionyldopa in the presence of cysteine or glutathione. Subsequent oxidation gives benzothiazine intermediates and finally to produce pheomelanin. Although three enzymes, TYR, TRP-1 and TRP-2 are involved in the melanogenesis pathway, tyrosinase is exclusively necessary for melanogenesis.(Pillaiyar et al., 2017)

Sequence and Features

Assembly Compatibility:

• 10
  COMPATIBLE WITH RFC[10]
• 12
  COMPATIBLE WITH RFC[12]
• 21
  COMPATIBLE WITH RFC[21]
• 23
  COMPATIBLE WITH RFC[23]
• 25
  COMPATIBLE WITH RFC[25]
• 1000
  COMPATIBLE WITH RFC[1000]

Functional characterization and result

We introduce the plasmid with TYR into the cells, where melanogen is produced as shown.

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Figure 1: (A)The blackening of HEK-293T cells at 24 h or 48 h post glucocorticoids treatment in microscope.(B)The blackening of HEK-293T cells at 24 h or 48 h post glucocorticoids treatment under the naked eye.

Reference

[1].Weikum ER, Knuesel MT, Ortlund EA, Yamamoto KR. Glucocorticoid receptor control of transcription: precision and plasticity via allostery. Nat Rev Mol Cell Biol. 2017 Mar;18(3):159-174. doi: 10.1038/nrm.2016.152. Epub 2017 Jan 5. PMID: 28053348; PMCID: PMC6257982.