11,12-dihydrolactaroviolin from edible mushroom Lactarius hatsudake Tanaka as a selective inhibitor of Mycobacterium tuberculosis.

Identifying functional food factors is crucial for food research. In particular, edible mushrooms contain natural antibacterial compounds, which can be used to develop functional foods. In this study, we isolated 11,12-dihydrolactaroviolin (dihydro-LAC), an antibacterial compound, from Lactarius hatsudake Tanaka (L. hatsudake), which selectively inhibited Mycobacterium tuberculosis (M. tuberculosis), including 80 drug-resistant strains, with a minimum inhibitory concentration (MIC) of 7.8 μg/mL. 500 μg/mL of dihydro-LAC showed no significant cytotoxicity to normal cells and enhanced the streptomycin clearance of M. tuberculosis. The results of molecular docking and molecular dynamics simulations showed that dihydro-LAC targets CmaA2 and MmaA2 enzymes in M. tuberculosis to interrupt cell wall synthesis. Further transcription and expression explorations validated the downregulation of the predicted targets. Furthermore, substrate accumulation occurred in mycolic acid biosynthesis in targeted metabonomics. This work offers valuable insights into the functional factors of edible mushrooms and provides a new functional food resource for specific populations.