Abstract:
:Chloropupukeananin and chloropestolides are novel metabolites of the plant endophyte Pestalotiopsis fici, showing antimicrobial, antitumor, and anti-HIV activities. Their highly complex and unique skeletons were generated from the coisolated pestheic acid (1) and iso-A82775C (10) based on our previous studies. Here, we identified the biosynthetic gene cluster iac of 10 and characterized an iacE encoded prenyltransferase. Deletion of iacE abolished iso-A82775C production, accumulated the prenyl group-lacking siccayne (2), and generated four new chloropestolides (3-6). Compounds 5 and 6 showed antibacterial effects against Staphylococcus aureus and Bacillus subtilis, and 5 was also cytotoxic to human tumor cell lines HeLa, MCF-7, and SW480. These results provided the first genetic and biochemical insights into the biosynthesis of natural prenylepoxycyclohexanes and demonstrated the feasibility for generation of diversified congeners by manipulating the biosynthetic genes of 10.
journal_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
Pan Y,Liu L,Guan F,Li E,Jin J,Li J,Che Y,Liu Gdoi
10.1021/acschembio.7b01059subject
Has Abstractpub_date
2018-03-16 00:00:00pages
703-711issue
3eissn
1554-8929issn
1554-8937journal_volume
13pub_type
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