A tyrosinase inhibitor from Corynebacterium tuberculostearicum (C. tuberculostearicum), a bacterium commonly found on human skin, may help safely treat hyperpigmentation.
After screening over 100 skin-derived bacteria, the researchers identified C. tuberculostearicum as a producer of a potent tyrosinase-inactivating compound. Their assays utilized tyrosinase from the mushroom Agaricus bisporus to confirm inhibition. Subsequent experiments pinpointed the active compound as cyclo (L-Pro-L-Tyr). The researchers then conducted three-dimensional (3D) docking simulations to elucidate how cyclo (L-Pro-L-Tyr) functions.
“Our goal was to understand how cyclo (L-Pro-L-Tyr) disrupts tyrosinase activity,” says lead researcher Assistant Professor Yuuki Furuyama from the Department of Applied Bioscience at the Tokyo University of Science in Tokyo, Japan, in a news release. “In melanin biosynthesis, tyrosinase initially converts L-tyrosine (L-Tyr) to dihydroxyphenylalanine (DOPA) quinone, which then transforms into DOPA chrome. Ultimately, DOPA chrome polymerizes to produce melanin. Our findings revealed that cyclo (L-Pro-L-Tyr) mimics L-Tyr, binding to and obstructing the substrate-binding pocket of mushroom tyrosinase. This interference renders the enzyme inactive.”
Dr. Furuyama adds that, “Our study is the first to identify and elucidate the mechanism of a tyrosinase inhibitor derived from a skin bacterium.”
Scientific literature supports the non-toxic nature of cyclo (L-Pro-L-Tyr) to human cells, underscoring its suitability as a skin probiotic for combating hyperpigmentation. Moreover, the metabolite exhibits additional beneficial properties such as antimicrobial, antioxidant, and anticancer activities, further enhancing its therapeutic potential across various applications. Of particular interest is the team’s success in extracting substantial quantities of cyclo (L-Pro-L-Tyr) from C. tuberculostearicum, paving the way for potential industrial-scale production. This capability is crucial for ensuring the financial feasibility of manufacturing active ingredients on a large scale.
“Before cyclo (L-Pro-L-Tyr) can be widely used further studies are essential,” Dr. Furuyama says. “Testing with human tyrosinase, which differs structurally from mushroom tyrosinase, is crucial. Detailed analyses of its mechanisms of action are also necessary to ensure efficacy and safety,”
The study is published in the International Journal of Molecular Sciences.
PHOTO CAPTION: Using docking simulations, recent study found that cyclo(L-Pro-L-Tyr) binds to the substrate-binding site of mushroom tyrosinase, obstructing the substrate pocket and preventing its activity.
PHOTO CREDIT: Yuuki Furuyama from Tokyo University of Science
