Journal
FRONTIERS IN CHEMISTRY
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fchem.2020.00270
Keywords
genome mining; Penicillium brocae; overexpression; global regulator PbrlaeA; silent gene cluster; polyketide; fumigatin chlorohydrin
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Funding
- NSFCShandong Joint Fund [U1906212, U1606403]
- Pilot National Laboratory for Marine Science and Technology [2018SDKJ0401-2, 2016ASKJ08-02]
- National Natural Science Foundation of China Major Project for Discovery of New Leading Compounds [81991522]
- National Science and Technology Major Project for Significant New Drugs Development [2018ZX09735004]
- Fundamental Research Funds for the Central Universities [201941001]
- China Postdoctoral Science Foundation [2017M622286]
- Taishan Scholar Youth Expert Program in Shandong Province [tsqn201812021]
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Overexpression of the PbrlaeA gene of the fungus Penicillium brocae HDN-12-143 resulted in the isolation of four compounds including fumigatin chlorohydrin (1), whose configuration has not been reported before, and one new compound iso-fumigatin chlorohydrin (2). All structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data, C-13 NMR calculations, and ECD calculations. Compounds 1 and 2 exhibited cytotoxic activity against HL-60 with IC50 of 18.63 and 24.83 mu M.
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