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Natural product diversity associated with the nematode symbionts Photorhabdus and Xenorhabdus

Abstract

Xenorhabdus and Photorhabdus species dedicate a large amount of resources to the production of specialized metabolites derived from non-ribosomal peptide synthetase (NRPS) or polyketide synthase (PKS). Both bacteria undergo symbiosis with nematodes, which is followed by an insect pathogenic phase. So far, the molecular basis of this tripartite relationship and the exact roles that individual metabolites and metabolic pathways play have not been well understood. To close this gap, we have significantly expanded the database for comparative genomics studies in these bacteria. Clustering the genes encoded in the individual genomes into hierarchical orthologous groups reveals a high-resolution picture of functional evolution in this clade. It identifies groups of genes—many of which are involved in secondary metabolite production—that may account for the niche specificity of these bacteria. Photorhabdus and Xenorhabdus appear very similar at the DNA sequence level, which indicates their close evolutionary relationship. Yet, high-resolution mass spectrometry analyses reveal a huge chemical diversity in the two taxa. Molecular network reconstruction identified a large number of previously unidentified metabolite classes, including the xefoampeptides and tilivalline. Here, we apply genomic and metabolomic methods in a complementary manner to identify and elucidate additional classes of natural products. We also highlight the ability to rapidly and simultaneously identify potentially interesting bioactive products from NRPSs and PKSs, thereby augmenting the contribution of molecular biology techniques to the acceleration of natural product discovery.

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Acknowledgements

Research in the Bode Laboratory was supported by a European research starting grant under grant agreement no. 311477. H.B.B. acknowledges the Deutsche Forschungsgemeinschaft for funding of the Impact II qTof mass spectrometer (INST 161/810-1). N.J.T. and Y.M.S. are supported by a Postdoctoral Research Fellowship from the Alexander von Humboldt Foundation. S.J.P. is supported by an Australian National Health and Medical Research Council (NHMRC) project grant APP1105522. T.P.S. is supported by an Australian NHMRC Career Development Fellowship. I.E. acknowledges financial support by the Deutsche Forschungsgemeinschaft (DFG-FOR 2251, project grant EB 285/2-1).

Author information

N.J.T., H.W., B.D., I.E. and H.B.B. designed the study. N.J.T., H.W., B.D., F.G., M.K., Y.-M.S., S.S., P.G., D.S.-I, S.J.P., T.P.S., I.E. and H.B.B. contributed to analysis of the data. N.J.T., H.W., B.D., Y.-M.S., S.J.P., T.P.S., I.E. and H.B.B. were involved in preparation of the manuscript.

Competing interests

The authors declare no competing financial interests.

Correspondence to Helge B. Bode.

Electronic supplementary material

  1. Supplementary Information

    Extra results regarding structure elucidation of compounds described in the text and Supplementary Tables 1 and 8–18, as well as Supplementary Figures 1–54 and Supplementary References.

  2. Life Sciences Reporting Summary

  3. Supplementary Table 2

    List of locus tags for all orthologous groups.

  4. Supplementary Table 3

    HOG gains at Node A.

  5. Supplementary Table 4

    HOG gains at Node B.

  6. Supplementary Table 5

    HOG gains at Node C.

  7. Supplementary Table 6

    Analysis of gene ontology pathways using the HOGs at a given node compared to the last common ancestor.

  8. Supplementary Table 7

    Custom database of known natural products.

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Further reading

Fig. 1: Evolutionary relationships of Xenorhabdus and Photorhabdus.
Fig. 2: Phyletic distribution of biosynthetic gene clusters in the Xenorhabdus/Photorhabdus family (XPF) clade.
Fig. 3: Network analysis of 30 Xenorhabdus and Photorhabdus strains.
Fig. 4
Fig. 5