Phomoxanthone A, a bioactive xanthone dimer isolated from the endophytic fungus Phomopsis sp., is a mitochondrial toxin weakening cellular respiration and electron transport chain activity by a fast breakup of the mitochondrial assembly. Here, a multi-disciplinary strategy has been developed and applied for identifying phomoxanthone A target(s) to fully address its mechanism of action, based on drug affinity response target stability and targeted limited proteolysis. Both approaches point to the identification of carbamoyl-phosphate synthase 1 as a major phomoxanthone A target in mitochondria cell lysates, giving also detailed insights into the ligand/target interaction sites by molecular docking and assessing an interesting phomoxanthone A stimulating activity on carbamoyl-phosphate synthase 1. Thus, phomoxanthone A can be regarded as an inspiring molecule for the development of new leads in counteracting hyperammonemia states.

中文翻译：

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氨基甲酸酯-磷酸合酶1作为新的靶标苯氧杂蒽酮A，一种生物活性真菌代谢物。

Phomoxanthone A，生物活性呫二聚体从内生真菌分离拟茎点霉sp。是一种线粒体毒素，通过快速破坏线粒体装配体而减弱细胞呼吸和电子转运链的活性。在此，基于药物亲和力响应靶标的稳定性和靶向的有限蛋白水解作用，已开发出一种多学科策略并将其应用于鉴定苯氧杂蒽酮A靶标以充分解决其作用机理。两种方法都将氨基甲酰磷酸合酶1鉴定为线粒体细胞裂解物中主要的苯氧杂蒽酮A靶标，还通过分子对接和评估有趣的苯氧杂蒽酮A对氨基甲酰磷酸合酶的活性，提供了对配体/靶标相互作用位点的详细了解。因此，苯氧杂蒽酮A可以被认为是在对抗高氨血症状态中开发新药物的一种启发性分子。