Halogenase-Targeted Genome Mining Leads to the Discovery of (±) Pestalachlorides A1a, A2a, and Their Atropisomers
Genome mining has become an important tool for discovering new natural products and identifying the cryptic biosynthesis gene clusters. Here, we utilized the flavin-dependent halogenase GedL as the probe in combination with characteristic halogen isotope patterns to mine new halogenated secondary me...
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| Main Authors: | , , , , , |
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| Format: | Book |
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MDPI AG,
2022-09-01T00:00:00Z.
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| Summary: | Genome mining has become an important tool for discovering new natural products and identifying the cryptic biosynthesis gene clusters. Here, we utilized the flavin-dependent halogenase GedL as the probe in combination with characteristic halogen isotope patterns to mine new halogenated secondary metabolites from our in-house fungal database. As a result, two pairs of atropisomers, pestalachlorides A1a (<b>1a</b>)/A1b (<b>1b</b>) and A2a (<b>2a</b>)/A2b (<b>2b</b>), along with known compounds pestalachloride A (<b>3</b>) and SB87-H (<b>4</b>), were identified from <i>Pestalotiopsis</i> <i>rhododendri</i> LF-19-12. A plausible biosynthetic assembly line for pestalachlorides involving a putative free-standing phenol flavin-dependent halogenase was proposed based on bioinformatics analysis. Pestalachlorides exhibited antibacterial activity against sensitive and drug-resistant <i>S. aureus</i> and <i>E. faecium</i> with MIC values ranging from 4 <i>μ</i>g/mL to 32 <i>μ</i>g/mL. This study indicates that halogenase-targeted genome mining is an efficient strategy for discovering halogenated compounds and their corresponding halogenases. |
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| Item Description: | 10.3390/antibiotics11101304 2079-6382 |