Chemical Interactions of Cryptic Actinomycete Metabolite 5‐Alkyl‐1,2,3,4‐tetrahydroquinolines through Aggregate Formation
Chemical Interactions of Cryptic Actinomycete Metabolite 5‐Alkyl‐1,2,3,4‐tetrahydroquinolines through Aggregate Formation
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隐性放线菌代谢物 5-烷基-1,2,3,4-四氢喹啉通过聚集体形成的化学相互作用
DOI：
10.1002/anie.201905970
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Kakeya Hideaki
中科院分区：
文献类型：
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作者：
Sugiyama Ryosuke;Nakatani Takahiro;Nishimura Shinichi;Takenaka Kei;Ozaki Taro;Asamizu Shumpei;Onaka Hiroyasu;Kakeya Hideaki
生物体通常以生物合成相关的同系物的混合物的形式产生次生代谢物。5-烷基-1，2，3，4-四氢喹啉类(5-烷基-1，2，3，4-四氢喹啉)(5aTHQs)是黑色链霉菌HEK616与肺曲霉菌TP-B0596共同培养时产生的亲脂小分子代谢物。5aTHQ的混合物形成聚集体，显示出增强的膜亲和力和生物活性。形成聚集体的能力和膜结合活性受烷基链的长度调节。具有长烷基链的聚集体太稳定，不能与脂膜融合。然而，如果将非活性的5aTHQ同系物与活性的同系物混合，混合物显示出更高的膜亲和力，使细胞能够进入并具有生物活性。因此，研究表明，生物合成途径中的马虎是功能合理的，因为代谢物表现出协同作用，通过这种途径可以产生微小的结构变化。
Organisms often produce secondary metabolites as a mixture of biosynthetically related congeners. However, why are metabolites with minor chemical variations produced simultaneously? 5‐Alkyl‐1,2,3,4‐tetrahydroquinolines (5aTHQs) are small, lipophilic metabolites produced by Streptomyces nigrescens HEK616 when cultured with Tsukamurella pulmonis TP‐B0596. A mixture of 5aTHQs forms aggregates that show enhanced membrane affinity and biological activity. The ability to form aggregates and membrane‐binding activity is regulated by the length of the alkyl chains. Aggregates with long alkyl chains were too stable to fuse with lipid membranes. However, if inactive 5aTHQ congener was mixed with active congener, the mixture showed increased membrane affinity, enabling cellular entry and biological activity. Therefore, it is shown that sloppiness in a biosynthetic pathway, by which minor structural variations can be produced, is functionally rational, as the metabolites show synergistic action.