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Issue 9, 2019
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Identification of the common biosynthetic gene cluster for both antimicrobial streptoaminals and antifungal 5-alkyl-1,2,3,4-tetrahydroquinolines

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Abstract

5-Alkyl-1,2,3,4-tetrahydroquinolines (5aTHQs) and streptoaminals (STAMs) are natural products isolated from the combined-culture of Streptomyces nigrescens HEK616 and Tsukamurella pulmonis TP-B0596. Despite their unique structures, their biosynthetic pathway has yet to be elucidated. In the present study, we conducted a feeding experiment using 13C-labeled acetates and demonstrated that 5aTHQs are likely synthesized by the action of polyketide synthase (PKS). Based on this observation, we identified the biosynthetic gene cluster for 5aTHQs. Interestingly, the same gene cluster was also responsible for the structurally-distinct STAMs. The gene cluster contains nine genes encoding one acyl carrier protein, two sets of ketosynthases (KSs) and chain length factors (CLFs), one aminotransferase/reductase bifunctional protein, two ketoreductases, and one thioesterase. KSs and CLFs are classified into the phylogenetically distinct clades from those of known type II PKSs. Heterologous expression of the biosynthetic genes and subsequent gene inactivation clearly indicated that all of the nine genes were required for the biosynthesis of both compounds. In the proposed biosynthetic pathway, chain elongation by PKS, reductive cleavage of a thioester bond, and subsequent transamination generate the core skeleton of both compounds. Differences in the oxidation states of the products result in a distinct cyclization mode to yield 5aTHQs and STAMs.

Graphical abstract: Identification of the common biosynthetic gene cluster for both antimicrobial streptoaminals and antifungal 5-alkyl-1,2,3,4-tetrahydroquinolines

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Publication details

The article was received on 15 Nov 2018, accepted on 17 Dec 2018 and first published on 24 Dec 2018


Article type: Paper
DOI: 10.1039/C8OB02846J
Citation: Org. Biomol. Chem., 2019,17, 2370-2378

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    Identification of the common biosynthetic gene cluster for both antimicrobial streptoaminals and antifungal 5-alkyl-1,2,3,4-tetrahydroquinolines

    T. Ozaki, R. Sugiyama, M. Shimomura, S. Nishimura, S. Asamizu, Y. Katsuyama, H. Kakeya and H. Onaka, Org. Biomol. Chem., 2019, 17, 2370
    DOI: 10.1039/C8OB02846J

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