Issue 9, 2019

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

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

  • This article is part of the themed collection: Biosynthesis

Supplementary files

Article information

Article type
Paper
Submitted
15 marras 2018
Accepted
17 joulu 2018
First published
24 joulu 2018

Org. Biomol. Chem., 2019,17, 2370-2378

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

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements