Journal
COMMUNICATIONS BIOLOGY
Volume 5, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s42003-022-03409-6
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Funding
- Ministry of Science and Technology of Taiwan [MOST 104-2320-B-001-019-MY2]
- Academia Sinica Core Facility and Innovative Instrument Project [AS-CFII-108-119]
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In a multi-omics analysis, bacterial polyynes were found to act as antifungal agents by inhibiting the Candida albicans polyyne resistance gene ERG10, providing a potential target for developing antifungal agents.
In a multi-omics analysis, bacterial polyynes are found to act as antifungal agents by inhibiting the Candida albicans polyyne resistance gene ERG10, the homolog of MasL encoding acetyl-CoA acetyltransferase. Bacterial polyynes are highly active natural products with a broad spectrum of antimicrobial activities. However, their detailed mechanism of action remains unclear. By integrating comparative genomics, transcriptomics, functional genetics, and metabolomics analysis, we identified a unique polyyne resistance gene, masL (encoding acetyl-CoA acetyltransferase), in the biosynthesis gene cluster of antifungal polyynes (massilin A 1, massilin B 2, collimonin C 3, and collimonin D 4) of Massilia sp. YMA4. Crystallographic analysis indicated that bacterial polyynes serve as covalent inhibitors of acetyl-CoA acetyltransferase. Moreover, we confirmed that the bacterial polyynes disrupted cell membrane integrity and inhibited the cell viability of Candida albicans by targeting ERG10, the homolog of MasL. Thus, this study demonstrated that acetyl-CoA acetyltransferase is a potential target for developing antifungal agents.
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