Melanin protects the skin – the body’s largest organ and a vital component of the immune system – from the damaging effects of ultraviolet (UV) radiation. When skin is exposed to UV radiation, melanin production is stimulated in melanocytes, with tyrosinase playing a key role in the biosynthetic pathway. However, disturbances in this pathway caused by UV exposure or aging can lead to excessive accumulation of melanin, resulting in hyperpigmentation. To combat this, tyrosinase inhibitors that suppress melanin synthesis have become valuable in the cosmetic industry. Unfortunately, some of these compounds, such as hydroquinone, have been found to be toxic to human skin, causing problems such as vitiligo-like symptoms and rashes. Consequently, hydroquinone is no longer recommended for use.
The growing demand for safer alternatives has sparked a race to discover tyrosinase inhibitors from microbes that produce compounds with low toxicity. Recently, researchers at Tokyo University of Science (TUS) identified a promising tyrosinase inhibitor from Corynebacterium tuberculostearicum (C. tuberculostearicum), a bacterium commonly found on human skin. The study, led by assistant professor Yuuki Furuyama from the Department of Applied Bioscience at TUS, was published in International Journal of Molecular Sciences on July 4, 2024. Co-authors Ms. Yuika Sekino and Prof. Kouji Kuramochi, also from TUS, contributed to the findings. Dr. Furuyama elaborated on their approach:Bacteria that inhabit our skin and evade immune system responses often become bystanders, neither benefiting us nor harming us. We chose to investigate metabolites produced by these common bacteria for their potential as tyrosinase inhibitors. These natural products derived from the skin exhibit low toxicity, making them inherently safer.”
After examining over 100 skin-derived bacteria, the team identified C. tuberculostearicum as a producer of a potent tyrosinase-inactivating compound. Their assays used tyrosinase from the mushroom Agaricus bisporus to confirm suspension. Subsequent experiments pinpointed the active compound as cyclo(L-Pro-L-Tyr). The researchers then conducted three-dimensional (3D) docking simulations to clarify how cyclo(L-Pro-L-Tyr) works.
“Our goal was to understand how cyclo(large-for-large-Tyr) disrupts tyrosinase activity.” Doctor Furuyama explained. “In melanin biosynthesis, tyrosinase is first converted large-tyrosine (large-Tyr) to dihydroxyphenylalanine (DOPA) quinone, which is then converted to chromium DOPA. Finally, the DOPA chromium polymerizes to produce melanin. Our findings revealed that cyclo(large-for-large-Tyr) imitates large-Tyr, binding and occlusion of the substrate-binding pocket of mushroom tyrosinase. This interference renders the enzyme inactiveDr. Furuyama emphasized the significance of their discovery:Our study is the first to identify and elucidate the mechanism of a tyrosinase inhibitor derived from a skin bacterium.”
The team is very optimistic about the possibilities of their discovery. Scientific literature supports the non-toxic nature of cyclo(L-Pro-L-Tyr) in human cells, underscoring its suitability as a skin probiotic to combat hyperpigmentation. In addition, the metabolite exhibits additional beneficial properties such as antimicrobial, antioxidant, and anticancer activities, further enhancing its therapeutic potential in various applications. Of particular interest is the group’s success in extracting significant amounts of cyclo(L-Pro-L-Tyr) from C. tuberculostearicum, paving the way for possible industrial-scale production. This capability is crucial to ensure the economic feasibility of large-scale production of active ingredients.
Despite the promising outlook, Dr. Furuyama acknowledges that there are significant hurdles to overcome before these natural active ingredients reach consumer shelves. It emphasizes the need for extensive research to precede the widespread adoption of cyclo(L-Pro-L-Tyr) in cosmetics. “before the cycle (large– Professional-LARGE-Tyr) can be widely used further studies are necessary. Testing with human tyrosinase, which is structurally different from mushroom tyrosinase, is crucial. Detailed analyzes of its mechanisms of action are also necessary to ensure efficacy and safety,” explains Dr. Furuyama.
Essentially, while the potential is significant, thorough scientific validation and understanding are prerequisites for the eventual application of cyclo(L-Pro-L-Tyr) in skin care products.
Source:
Journal Reference:
Sekino, Y., et al. (2024). Cyclo(l-Pro-l-Tyr) Isolated from Human Skin Commensal Corynebacterium tuberculostearicum Inhibits Tyrosinase. International Journal of Molecular Sciences. doi.org/10.3390/ijms25137365.
