Comoclathrin, a novel potent skin-whitening agent produced by endophytic Comoclathris strains associated with Andalusia desert plants

• Published in: Scientific reports Vol. 12; no. 1; pp. 1649 - 12
• Main Authors: Georgousaki, Katerina, González-Menéndez, Victor, Tormo, José R., Tsafantakis, Nikolaos, Mackenzie, Thomas A., Martín, Jesús, Gumeni, Sentiljana, Trougakos, Ioannis P., Reyes, Fernando, Fokialakis, Nikolas, Genilloud, Olga
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31.01.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/1647/320; 631/1647/767/2202; 631/92; 631/92/349; 639/638/403/936; A549 Cells; Ascomycota - genetics; Ascomycota - metabolism; Bioassays; Cell Survival - drug effects; Chromatography; Cytotoxicity; Desert Climate; Desert plants; Endophytes; Endophytes - genetics; Endophytes - metabolism; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - toxicity; Enzymes; Fermentation; Fibroblasts; Fungi; Hep G2 Cells; Humanities and Social Sciences; Humans; Kojic acid; Mass spectrometry; MCF-7 Cells; Metabolites; Metabolome; Metabolomics; Microorganisms; Monophenol Monooxygenase - antagonists & inhibitors; Monophenol Monooxygenase - metabolism; multidisciplinary; New species; NMR; Nuclear magnetic resonance; Phylogenetics; Phylogeny; Plants - microbiology; Science; Science (multidisciplinary); Scientific imaging; Secondary metabolites; Skin; Skin Lightening Preparations - isolation & purification; Skin Lightening Preparations - pharmacology; Skin Lightening Preparations - toxicity; Tumor cell lines
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-05448-9

As part of our screening program for the discovery of molecules of microbial origin with skin-whitening activity, 142 diverse fungal endophytes from a wide variety of Andalusia arid plants were screened, applying the OSMAC approach. The fungal strains CF-090361 and CF-090766, isolated from xerophytic plants, were selected as the most promising, while phylogenetic analysis revealed that both strains could represent a new species within the genus Comoclathris . 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 strains and fermentation conditions, and to identify potential bioactive secondary metabolites. Bioassay-guided purification of the main active components led to the isolation of three new compounds ( 1–3 ), along with the known compounds graphostrin B ( 4 ) and brevianamide M ( 5 ). Compound 1 (Comoclathrin) demonstrated the strongest anti-tyrosinase activity (IC 50 0.16 μΜ), which was 90-times higher than kojic acid (IC 50 14.07 μΜ) used as positive control. Additionally, comoclathrin showed no significant cytotoxicity against a panel of cancer cell lines (HepG2, A2058, A549, MCF-7 and MIA PaCa-2) and normal BJ fibroblasts. These properties render comoclathrin an excellent development candidate as whitening agent.