Light‐Triggered In Situ Biosynthesis of Artificial Melanin for Skin Protection

Tyrosinase‐mediated melanin synthesis is an essential biological process that can protect skin from UV radiation and radical species. This work reports on in situ biosynthesis of artificial melanin in native skin using photoactivatable tyrosinase (PaTy). The I41Y mutant of Streptomyces avermitilis tyrosinase (SaTy) shows enzymatic activity comparable to that of wild‐type SaTy. This Y41 is replaced with photocleavable o‐nitrobenzyl tyrosine (ONBY) using the introduction of amber codon and ONBY‐tRNA synthetase/tRNA pairs. The ONBY efficiently blocks the active site and tyrosinase activity is rapidly recovered by the photo‐cleavage of ONBY. The activated PaTy successfully oxidizes L‐tyrosine and tyramine‐conjugated hyaluronic acid (HA_T) to synthesize melanin particles and hydrogel, respectively. To produce artificial melanin in living tissues, PaTy is encapsulated into lipid nanoparticles as an artificial melanosome. Using liposomes containing PaTy (PaTy_Lip), PaTy is transdermally delivered into ex vivo porcine skin and in vivo mouse skin tissues, thus achieving the in situ biosynthesis of artificial melanin for skin tissue protection under UV irradiation. The results of this study demonstrate that this biomimetic system can recapitulate the biosynthetic analogs of naturally occurring melanin. It should therefore be considered to be a promising strategy for producing protective biological molecules within living systems for tissue protection.