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Genome mining reveals uncommon alkylpyrones as type III PKS products from myxobacteria

  • Joachim J. Hug
  • Fabian Panter
  • Daniel Krug
  • Rolf MüllerEmail author
Natural Products - Original Paper

Abstract

Type III polyketide synthases (PKSs) are comparatively small homodimeric enzymes affording natural products with diverse structures and functions. While type III PKS biosynthetic pathways have been studied thoroughly in plants, their counterparts from bacteria and fungi are to date scarcely characterized. This gap is exemplified by myxobacteria from which no type III PKS-derived small molecule has previously been isolated. In this study, we conducted a genomic survey of myxobacterial type III PKSs and report the identification of uncommon alkylpyrones as the products of type III PKS biosynthesis from the myxobacterial model strain Myxococcus xanthus DK1622 through a self-resistance-guided screening approach focusing on genes encoding pentapetide repeat proteins, proficient to confer resistance to topoisomerase inhibitors. Using promoter-induced gene expression in the native host as well as heterologous expression of biosynthetic type III PKS genes, sufficient amounts of material could be obtained for structural elucidation and bioactivity testing, revealing potent topoisomerase activity in vitro.

Keywords

Myxobacteria Genome mining Natural products Type III polyketide synthase Self-resistance 

Notes

Acknowledgements

The authors thank Alexander Popoff for recording the NMR spectra of the alkylpyrones, Viktoria Schmitt and Jennifer Herrmann for performing bioactivity assays, Ronald Garcia for microbiological assistance and Nestor Zaburannyi for bioinformatic support. Joachim J. Hug was supported by a PhD fellowship of the Boehringer Ingelheim Fonds.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

10295_2018_2105_MOESM1_ESM.docx (2 mb)
Supplementary material 1 (DOCX 2042 kb)

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Copyright information

© Society for Industrial Microbiology and Biotechnology 2018

Authors and Affiliations

  1. 1.Department Microbial Natural Products, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS)Helmholtz Centre for Infection Research (HZI)SaarbrückenGermany
  2. 2.Department of PharmacySaarland UniversitySaarbrückenGermany
  3. 3.German Center for Infection Research (DZIF)Partner Site Hannover-BraunschweigGermany

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