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 (1a)/A1b (1b) and A2a (2a)/A2b (2b), along with known compounds pestalachloride A (3) and SB87-H (4), were identified from Pestalotiopsis rhododendri 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 S. aureus and E. faecium with MIC values ranging from 4 μg/mL to 32 μg/mL. This study indicates that halogenase-targeted genome mining is an efficient strategy for discovering halogenated compounds and their corresponding halogenases.

中文翻译：

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卤素酶靶向基因组挖掘导致 (±) Pestalchlorides A1a、A2a 及其阻转异构体的发现

基因组挖掘已成为发现新天然产物和识别隐蔽生物合成基因簇的重要工具。在这里，我们利用黄素依赖性卤素酶 GedL 作为探针，结合特征卤素同位素模式，从我们的内部真菌数据库中挖掘新的卤代次级代谢产物。因此，两对阻转异构体 pestalchlorides A1a ( 1a )/A1b ( 1b ) 和 A2a ( 2a )/A2b ( 2b ) 以及已知化合物 pestalchloride A ( 3 ) 和 SB87-H ( 4 ) 从杜鹃 花LF-19-12。基于生物信息学分析，提出了一条合理的 pestalchloride 生物合成装配线，该装配线涉及假定的独立苯酚黄素依赖性卤化酶。Pestalchlorides 对敏感和耐药的金黄色葡萄球菌和粪肠球菌表现出抗菌活性，MIC 值范围为 4 μ g/mL 至 32 μ g/mL。该研究表明，以卤化酶为目标的基因组挖掘是发现卤代化合物及其相应卤化酶的有效策略。