Multiscale engineering of enhanced melanin production in Streptomyces sp. for anticancer activity against skin melanoma

In the present study, using a multiscale engineering approach, the coral mucus-derived actinomycetes Streptomyces sp. was isolated and used for enhanced melanin production. Initially, the culture conditions were optimized for melanin production by varying the carbon and nitrogen sources and environmental factors using a Central Composite Design. The results exhibited that the highest melanin production (15.8 mu g/0.1 mL of medium) was observed at glycerol (5 g/L), yeast extract (5 g/L), incubation time (108 h), pH 7 at 35 degrees C, and characterized using solid-state NMR analysis. Based on the Gene Expression Omnibus database for skin cancer, the PI3K/Akt/ mTOR signaling pathway was significantly enriched in skin cancer samples compared with normal tissue samples. The in vitro anticancer studies demonstrated that the oxidative stress damages the mitochondrial membrane, and consequently regulates the intrinsic apoptosis signaling pathway in B16F10 skin cancer cells at 7 and 10 mu g/ mL of melanin. Further, melanin downregulates the marker proteins of oncogenic signaling pathways such as PI3K, Akt, and mTOR in B16F10 cells. In conclusion, the melanin could bean excellent anticancer agent targeting the central node PI3K/Akt/mTOR signaling pathway.