Chemical Interactions of Cryptic Actinomycete Metabolite 5‐Alkyl‐1, 2, 3, 4‐tetrahydroquinolines through Aggregate Formation. (7th August 2019)

• Record Type: Journal Article
• Authors: Sugiyama, Ryosuke; Nakatani, Takahiro; Nishimura, Shinichi; Takenaka, Kei; Ozaki, Taro; Asamizu, Shumpei; Onaka, Hiroyasu; Kakeya, Hideaki
• Is Part Of: Angewandte Chemie. Volume 131:Number 38(2019)
• Page Start: 13620
• Page End: 13625
• Publication Date: 2019-08-07
• Subjects: Aggregate -- Kombinierte Kulturen -- Lipophile Metabolite -- Membranen -- Naturstoffe; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201905970
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: 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. Abstract : Kleiner Regulator : 5aTHQs sind kleine lipophile Metaboliten, die durch Streptomyces nigrescens HEK616 in einer kombinierten Kultur produziert werden. Sie bilden membranaktive Aggregate, durch die biologische Aktivitäten reguliert werden können.