Melanin is a pigment that plays a crucial role in protecting the skin, the largest organ in the human body and a key player in the immune system, against harmful ultraviolet (UV) radiation. When skin encounters UV rays, melanocytes stimulate the production of melanin, with the enzyme tyrosinase being essential in this biosynthetic process. However, disruptions in this process, which can occur due to UV exposure or aging, may lead to an overproduction of melanin, resulting in conditions like hyperpigmentation. To combat this, tyrosinase inhibitors that limit melanin formation have become sought-after in the cosmetic sector. Unfortunately, some of these inhibitors, like hydroquinone, have been found to be harmful to the skin, causing adverse effects such as symptoms resembling vitiligo and rashes. Because of these risks, hydroquinone is now discouraged for use.
In response to the growing need for safer alternatives, researchers are racing to find tyrosinase inhibitors derived from microbes that produce less toxic compounds. Recently, a team from Tokyo University of Science (TUS) discovered an effective tyrosinase inhibitor sourced from Corynebacterium tuberculostearicum (C. tuberculostearicum), a bacterium that typically resides on human skin. This study, overseen by Assistant Professor Yuuki Furuyama from TUS’s Department of Applied Bioscience, was published in the International Journal of Molecular Sciences on July 4, 2024. The research included contributions from co-authors Ms. Yuika Sekino and Prof. Kouji Kuramochi, also from TUS. Dr. Furuyama described their research strategy: “We decided to explore metabolites produced by commensal bacteria on our skin, which often avoid triggering immune responses. These natural compounds demonstrate low toxicity, making them safer options.”
After examining over 100 bacteria found on skin, the researchers singled out C. tuberculostearicum as a source of a powerful compound that inactivates tyrosinase. To verify the inhibition, they used tyrosinase sourced from the mushroom Agaricus bisporus. Further tests revealed that the active component was cyclo(L-Pro-L-Tyr). The team then employed three-dimensional (3D) docking simulations to investigate how cyclo(L-Pro-L-Tyr) operates.
“Our objective was to comprehend how cyclo(L-Pro-L-Tyr) impairs tyrosinase function,” Dr. Furuyama articulated. “In melanin production, tyrosinase first turns L-tyrosine (L-Tyr) into dihydroxyphenylalanine (DOPA) quinone, which then converts into DOPA chrome. Ultimately, DOPA chrome polymerizes resulting in melanin. Our study discovered that cyclo(L-Pro-L-Tyr) resembles L-Tyr, binding to and blocking the substrate-binding pocket of mushroom tyrosinase, which leads to the enzyme’s inactivity.” Dr. Furuyama highlighted the importance of their findings: “This research represents the first time a tyrosinase inhibitor derived from skin bacteria has been identified and its mechanism elucidated.”
The research team is very optimistic about the implications of their discovery. Existing scientific literature supports the non-toxic nature of cyclo(L-Pro-L-Tyr) for human cells, indicating its potential as a skin probiotic that could aid in addressing hyperpigmentation. Furthermore, the metabolite presents additional advantages, including antimicrobial, antioxidant, and anticancer properties, which expand its potential therapeutic uses. Particularly notable is the success in extracting considerable amounts of cyclo(L-Pro-L-Tyr) from C. tuberculostearicum, which sets the stage for potential industrial-scale production—an essential factor for achieving the economic viability of making active ingredients in larger quantities.
However, Dr. Furuyama is aware that substantial challenges must be addressed before these natural ingredients can be offered to consumers. He stresses the need for thorough research prior to the broad adoption of cyclo(L-Pro-L-Tyr) in cosmetic products. “Before cyclo(L-Pro-L-Tyr) can be widely used, further investigations are critical. Testing with human tyrosinase, which has a different structure than mushroom tyrosinase, is vital. We also need detailed analyses of its mechanisms of action to ensure both effectiveness and safety,” Dr. Furuyama elaborated.
In summary, while the prospects for cyclo(L-Pro-L-Tyr) are bright, comprehensive scientific validation and understanding are necessary for its future use in skincare formulations.
