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It can inhibit the enzyme responsible for excess melanin accumulation, say researchers at Tokyo University of Science.
August 28, 2024
By: Christine Esposito
Editor-in-Chief
Researchers from Tokyo University of Science (TUS) have identified what they say is a promising tyrosinase inhibitor from Corynebacterium tuberculostearicum (C. tuberculostearicum), a bacterium commonly found on human skin. Tyrosinase inhibitors suppress melanin synthesis.
Their work, led by Assistant Professor Yuuki Furuyama from the Department of Applied Bioscience at TUS, was published last month in the International Journal of Molecular Sciences. Co-authors included Yuika Sekino and Prof. Kouji Kuramochi, also from TUS.
“Bacteria that reside on our skin and evade immune responses often become commensals, neither benefiting nor harming us. We chose to investigate metabolites produced by these commensal bacteria for their potential as tyrosinase inhibitors. These natural skin-derived products exhibit low toxicity, making them inherently safer,” said Dr. Furuyama.
The team screened more than 100 skin-derived bacteria, during which it 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.
The goal was to understand how cyclo(L-Pro-L-Tyr) disrupts tyrosinase activity, according to Dr. Furuyama.
He said the findings revealed that cyclo(L-Pro-L-Tyr) mimics L-Tyr, binding to and obstructing the substrate-binding pocket of mushroom tyrosinase, which renders the enzyme inactive.
“Our study is the first to identify and elucidate the mechanism of a tyrosinase inhibitor derived from a skin bacterium,” asserted Dr. Furuyama.
The team is optimistic about the potential of their discovery; 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, it says. Moreover, the metabolite exhibits additional beneficial properties (antimicrobial, antioxidant for example) 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—which would be crucial for ensuring the financial feasibility of manufacturing active ingredients on a large scale.
And Dr. Furuyama noted additional work remains.
“Before cyclo(L-Pro-L-Tyr) can be widely used further studies are essential. 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,” said Dr. Furuyama.
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