Natural product diversity associated with the nematode symbionts Photorhabdus and Xenorhabdus

Authors: TOBIAS, NICHOLAS - Goethe University; WOLFF, HENDRIK - Goethe University; DJAHANSCHIRI, BARDYA - Goethe University; GRUNDMANN, FLORIAN - Goethe University; KRONENWERTH, MAX - Goethe University; SHI, Y - Non ARS Employee; SIMONYI, SVENJA - Goethe University; GRUN, PETER - Goethe University; Shapiro Ilan, David; PIDOT, SACHA - Melbourne University; STINEAR, TIMOTHY - Melbourne University; EBERSBERGER, INGO - Melbourne University; BODE, HELGE - Goethe University

Submitted to: Nature Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/30/2017
Publication Date: 12/11/2017
Citation: Tobias, N.J., Wolff, H., Djahanschiri, B., Grundmann, F., Kronenwerth, M., Shi, Y.M., Simonyi, S., Grun, P., Shapiro Ilan, D.I., Pidot, S.J., Stinear, T.P., Ebersberger, I., Bode, H.B. 2017. Natural product diversity associated with the nematode symbionts Photorhabdus and Xenorhabdus. Nature Microbiology. 2(12):1676-1685. https://doi:10.1038/s41564-017-0039-9.
DOI: https://doi.org/10.1038/s41564-017-0039-9

Interpretive Summary: Bacteria known as Xenorhabdus and Photorhabdus are considered beneficial. They are natural symbiotic organisms that are associated with beneficial insect-killing nematodes. These nematodes are used as environmentally friendly bio-insecticides. These bacteria produce certain by-products (metabolites) that can also be beneficial. For example, some of the metabolites are anti-fungal and are therefore being studied as potential new environmentally friendly fungicides. Identifying new and effective metabolites from Xenorhabdus and Photorhabdus bacteria can be difficult. In this study, a comparative genomic approach was used in conjunction with metabolite profiling. The study involved a wide array of bacteria including one called Xenorhabdus szentirmaii, which was observed to produce potent metabolites with strong anti-fungal activity. The results revealed that the combined approach (of genomic and metabolite profiling may be a powerful tool in screening for novel metabolites. The more efficient and broad approach to identifying novel metabolites could expedite discovery of new beneficial natural compounds (such as new fungicides and insecticides).

Technical Abstract: Xenorhabdus and Photorhabdus species produce many specialized metabolites derived from non-ribosomal synthetase (NRPS) or polyketide synthase (PKS) with utilities in maintaining a complex life cycle. Both bacteria undergo a symbiosis with nematodes which is then 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 is only poorly understood. To close this gap, we have increased the data base for comparative genomics studies by 51 percent. 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 probably account for the niche specificity of these bacteria. Photorhabdus and Xenorhabdus appear very similar on the DNA sequence level, which indicates their close evolutionary relationships. Yet, high-resolution mass spectrometry analyses revealed distinct chemical profiles for the two taxa. Molecular network reconstruction identified several previously unknown metabolite classes, including the xefoampeptides and tilivalline. We further demonstrate that applying genomic and metabolomic methods in a complimentary manner can be used in order to rapidly and simultaneously identify potentially interesting bioactive products from NRPSs and PKSs, bypassing the need for time consuming molecular biology techniques and thereby accelerating natural product discovery.