Thermolides, Potent Nematocidal PKS-NRPS Hybrid Metabolites from Thermophilic Fungus Talaromyces thermophilus
Thermolides, Potent Nematocidal PKS-NRPS Hybrid Metabolites from Thermophilic Fungus Talaromyces thermophilus
复制标题
Thermolides，来自嗜热真菌 Talaromyces thermophilus 的强效杀线虫 PKS-NRPS 混合代谢物
DOI：
10.1021/ja3104044
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发表时间：
2012-12-19
影响因子：
15
通讯作者：
Niu, Xue-Mei
中科院分区：
文献类型：
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作者：
Guo, Ji-Peng;Zhu, Chun-Yan;Niu, Xue-Mei
大环PKS-NRPS杂化代谢产物是一类独特的天然产物，主要来源于细菌，具有广泛而突出的生物活性。然而，它们在真菌中的分布很少被报道，关于它们的杀线虫活性的报道也很少。在这里，我们描述了一类史无前例的PKS-NRPS杂化代谢物，具有13个成员的含内酰胺的大内酯，来自嗜热真菌Talarmyces thermophilus的热分子化合物A F(1-6)。结果表明，化合物1和2对3种臭名昭著的线虫均有较强的抑制活性，其LC_(50)值为0.5-1微克/毫升，与市售阿维菌素相当。本工作为杀线虫药物的发现提供了一类新的先导化合物。
Macrocyclic PKS-NRPS hybrid metabolites represent a unique family of natural products mainly from bacteria with broad and outstanding biological activities. However, their distribution in fungi has rarely been reported, and little has been reported regarding their nematocidal activity. Here we describe an unprecedented class of PKS-NRPS hybrid metabolites possessing a 13-membered lactam-bearing macrolactone, thermolides A F (1-6) from a thermophilic fungus Talaromyces thermophilus. We showed that 1 and 2 displayed potent inhibitory activity against three notorious nematodes with LC50 values of 0.5-1 mu g/mL, as active as commercial avermectins. This work provided a new class of promising lead compounds for nematocide discovery.