Format

Send to

Choose Destination
Nat Chem Biol. 2019 Apr;15(4):331-339. doi: 10.1038/s41589-019-0246-1. Epub 2019 Mar 18.

Dual phenazine gene clusters enable diversification during biosynthesis.

Author information

1
Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe Universität Frankfurt, Frankfurt am Main, Germany.
2
Institute of Microbiology, Eidgenössische Technische Hochschule Zurich, Zurich, Switzerland.
3
Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe Universität Frankfurt, Frankfurt am Main, Germany. h.bode@bio.uni-frankfurt.de.
4
Buchmann Institute for Molecular Life Sciences, Goethe Universität Frankfurt, Frankfurt am Main, Germany. h.bode@bio.uni-frankfurt.de.

Abstract

Biosynthetic gene clusters (BGCs) bridging genotype and phenotype continuously evolve through gene mutations and recombinations to generate chemical diversity. Phenazine BGCs are widespread in bacteria, and the biosynthetic mechanisms of the formation of the phenazine structural core have been illuminated in the last decade. However, little is known about the complex phenazine core-modification machinery. Here, we report the diversity-oriented modifications of the phenazine core through two distinct BGCs in the entomopathogenic bacterium Xenorhabdus szentirmaii, which lives in symbiosis with nematodes. A previously unidentified aldehyde intermediate, which can be modified by multiple enzymatic and non-enzymatic reactions, is a common intermediate bridging the pathways encoded by these BGCs. Evaluation of the antibiotic activity of the resulting phenazine derivatives suggests a highly effective strategy to convert Gram-positive specific phenazines into broad-spectrum antibiotics, which might help the bacteria-nematode complex to maintain its special environmental niche.

PMID:
30886436
DOI:
10.1038/s41589-019-0246-1
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center