Scientists see new compound from skin bacteria safely targeting hyperpigmentation

20 Aug 2024 --- Researchers at Tokyo University of Science (TUS) say they are “the first” to isolate a promising tyrosinase inhibitor from the common skin resident Corynebacterium tuberculostearicum. Personal Care Insights speaks to assistant professor Yuuki Furuyama to learn about the discovery’s implications and applications for combating hyperpigmentation caused by excess melanin production due to UV exposure or aging. 

The study in the International Journal of Molecular Sciences notes that melanin protects the skin from UV radiation, however, disruptions in its pathway may cause hyperpigmentation.

Cosmetic solutions to hyperpigmentation often aim to inhibit tyrosinase, as it suppresses melanin synthesis, say TUS. However, controversial compounds like hydroquinone in skin-lightening cosmetics have been found to be toxic, causing vitiligo-like symptoms and rashes.

The study authors note a “growing interest in identifying compounds derived from microorganisms as potential tyrosinase inhibitors,” such as kojic acid from the fungi Aspergillus oryzae is less harmful than its synthetic counterpart. 

“Indeed, soil and marine bacteria produce a diverse array of these inhibitors. Moreover, probiotic bacteria such as Lactobacillus spp. and Bifidobacterium spp. exhibit tyrosinase inhibitory activity; however, the associated active compounds and underlying inhibitory mechanisms have not yet been elucidated. Moreover, a diverse range of bacteria inhabit the human skin — the largest organ and the outermost layer of the immune system.”

Cyclo(L-Pro-L-Tyr) inhibits tyrosinase, potentially offering a safer solution for hyperpigmentation treatment.Study leader Furuyama and his team from Tokyo University of Science sought a safe and effective solution to hyperpigmentation by screening over 100 skin-derived bacteria. They identified C. tuberculostearicum as a producer of a potent tyrosinase-inactivating compound. Their assays, using tyrosinase from the mushroom Agaricus bisporus, confirmed inhibition.

According to Furuyama, skin-dwelling bacteria that avoid immune responses frequently evolve into commensals, neither helping nor hurting humans, which is why he decided to look into these commensal bacteria’s metabolites to see if they could act as tyrosinase inhibitors. Natural skin-derived products show low toxicity, making them inherently safer.

Can you briefly explain the findings of your research and implications for the personal care industry?
Furuyama: We identified a promising tyrosinase inhibitor from C. tuberculostearicum, and we revealed that one of the active compounds is cyclo(L-Pro-L-Tyr). Previous studies support the non-toxic nature of cyclo(L-Pro-L-Tyr) in human cells. Therefore, this bacterium has potential utility as a skin probiotic to suppress hyperpigmentation.

How did you screen skin bacteria for tyrosinase inhibitors?
Furuyama: Skin microbiota stocks were randomly selected and cultured overnight in a liquid medium under aerobic conditions. The culture broths were filtered and screened based on tyrosinase inhibitory activity. We found that a sample of sterile culture supernatant significantly inhibited the formation of dopa chrome by tyrosinase. Natural skin-derived products show low toxicity, making them inherently safer.

What makes cyclo(L-Pro-L-Tyr) effective in blocking tyrosinase?
Furuyama: The tyrosine residue of cyclo(L-Pro-L-Tyr) is important for inhibitory activity. The results of 3D docking simulations indicated that cyclo(L-Pro-L-Tyr) was bound to the tyrosinase active site and occupied the substrate pocket.

How is cyclo(L-Pro-L-Tyr) safe and effective for tackling hyperpigmentation?
Furuyama: Some studies reported that cyclo(L-Pro-L-Tyr) is nontoxic to normal human cells. In addition, we also confirmed that cyclo(L-Pro-L-Tyr) shows low cytotoxicity in human cells by using our own cytotoxicity assay. As for the effectiveness of cyclo(L-Pro-L-Tyr), there are significant hurdles to overcome before these natural active ingredients can reach consumer shelves. Further evaluation of human-derived tyrosinases and a more detailed analysis of their mechanisms of action are required.

What are the challenges in producing cyclo(L-Pro-L-Tyr) on a large scale?
Furuyama: One of the simplest reactions to synthesize dipeptides is the dehydrative amide coupling of two amino acids using condensation reagents. However, this reaction needs an amount of reagents, a complicated experimental procedure and removing byproducts derived from condensation reagents. On the other hand, with C. tuberculostearicum, relatively large amounts of cyclo(L-Pro-L-Tyr) can be easily obtained simply by just culturing.

By Venya Patel