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Chemical Interactions of Cryptic Actinomycete Metabolite 5‐Alkyl‐1,2,3,4‐tetrahydroquinolines through Aggregate Formation
Author(s) -
Sugiyama Ryosuke,
Nakatani Takahiro,
Nishimura Shinichi,
Takenaka Kei,
Ozaki Taro,
Asamizu Shumpei,
Onaka Hiroyasu,
Kakeya Hideaki
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201905970
Subject(s) - chemistry , alkyl , metabolite , membrane , congener , actinomycetales , stereochemistry , biochemistry , biological activity , secondary metabolite , streptomyces , bacteria , organic chemistry , biology , in vitro , gene , genetics
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.