Chemical Interactions of Cryptic Actinomycete Metabolite 5‐Alkyl‐1,2,3,4‐tetrahydroquinolines through Aggregate Formation

Abstract

Organisms often produce secondary metabolites as amixture 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. Am ixture of 5aTHQs forms aggregates that showenhanced membrane affinity and biological activity.T he ability to form aggregates and membranebinding activity is regulated by the length of the alkylc hains. Aggregates with long alkylc hains were too stable to fuse with lipid membranes.H owever,i fi nactive 5aTHQ congener was mixed with active congener,t he mixture showed increased membrane affinity,e nabling cellular entry and biological activity.Therefore,itisshown that sloppiness in abiosynthetic pathway,b yw hichm inor structural variations can be produced, is functionally rational, as the metabolites show synergistic action.