# Discovery of Tyrosinase Inhibitors from Lysinibacillus sp. JNUCC 52 via Genome Mining, Secondary Metabolites Profiling, and In Silico Analysis

## TL;DR

Researchers found a compound from a Lysinibacillus strain that strongly inhibits tyrosinase, an enzyme involved in melanin production, suggesting potential for therapeutic and cosmetic use.

## Contribution

The study identifies cyclo(L-Pro-L-Leu) as a potent tyrosinase inhibitor from Lysinibacillus sp. JNUCC 52, supported by in silico and experimental analyses.

## Key findings

- Cyclo(L-Pro-L-Leu) showed strong tyrosinase inhibition with an IC50 of 79.5 ± 2.3 μM.
- In silico analysis confirmed favorable drug-like properties and stable binding to tyrosinase.
- Lysinibacillus sp. JNUCC 52 is a promising source of bioactive secondary metabolites.

## Abstract

Tyrosinase is a key enzyme in melanin biosynthesis, and natural inhibitors have potential therapeutic and cosmetic applications. Lysinibacillus sp. JNUCC 52, a member of the Bacillaceae family, shows potential for producing bioactive secondary metabolites. However, the tyrosinase inhibitory potential of metabolites from this strain has not been previously reported. This study investigates its genomic features, secondary metabolites, and tyrosinase inhibitory activity to identify promising enzyme inhibitors. Integrated COG, GO, and KEGG annotation revealed a metabolically robust network supporting secondary metabolite biosynthesis. Chemical investigation of the ethyl acetate extract yielded five known compounds, among which cyclo(L-Pro-L-Leu) displayed the strongest tyrosinase inhibition (IC50 = 79.5 ± 2.3 μM), whereas uracil showed weaker activity. In silico ADMET and drug-likeness analyses suggested favorable pharmacokinetic properties and compliance with major drug-likeness rules for cyclo(L-Pro-L-Leu). Molecular docking and molecular dynamics simulations demonstrated stable binding to mushroom tyrosinase (mTYR) and human TYRP1, supported by MM/GBSA and residue decomposition analyses identifying key stabilizing residues. Together, these results provide mechanistic insight into tyrosinase inhibition and highlight cyclo(L-Pro-L-Leu) as a minimal lead-like scaffold, while establishing strain JNUCC 52 as a promising microbial source of bioactive metabolites.