Bio-guided isolation of tyrosinase inhibitors produced by Amycolatopsis strain derived from the Greek ecosystem

Actinobacteria from Greek ecosystems are renowned for their ability to produce bioactive compounds, yet their rich chemodiversity remains largely unexplored [ 1 ]. As part of our screening project for the discovery of molecules of microbial origin with skin-whitening activity, 1000 isolates originating from the Greek natural environment and belonging to the ATHUBA collection (Athens University Bacterial & Archaea Culture Collection) were investigated. The microbial strain Q6 was selected as the most promising, while phylogenetic analysis revealed that it could represent a new species within the genus Amycolatopsis . The effect of different fermentation conditions on the production of tyrosinase inhibitory activity was examined, in order to identify the optimum cultivation conditions. LCMS based metabolomics was applied to determine significant differences between the fermentation conditions, and to identify potential bioactive secondary metabolites. A customized bio-guided workflow was then applied, which combined a high-throughput dereplication and molecular networking method (UHPLC-HRMS), along with tyrosinase-based HPTLC-bioautography and the bioactivity of each fraction. Bioassay-guided purification of the main active components led to the isolation and structure elucidation of key compounds using 1&2D NMR. The ultimate goal of this study is the targeted isolation and identification of bioactive compounds, which can be integrated into cosmeceutical formulations. The latter findings highlight the significant potential for exploiting the Hellenic microbial diversity in the realm of anti-aging research. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany