Nematodes produce a blend of small molecules named ascarosides or NDMM (Nematode Derived Modular Metabolites) which consists of a dideoxy sugar and fatty acid derived side chain. The first ascaroside ascr#1 was identified from the liquid culture medium of the model organism C. elegans and later, ascr#2 together with ascr#3 were discovered and shown to trigger the entrance into a stress resistant, so called “Dauer” stage. Recently, ascarosides were found to modulate many aspects of nematodes including larval development, mating and social behaviors and very importantly they are widely conserved in nematodes.
Using NMR and organic synthesis, a panel of complex ascarosides was discovered from P. pacificus which are unique from those derived from C. elegans (Bose et al. 2012). The novel compounds npar#1 was found to regulate dauer formation and the homodimeric ascaroside dasc#1 was capable of inducing a complex mouth formation (Eurystomatous). Interestingly, a series of primary metabolic building blocks were incorporated into their chemical architectures, for instance, pentamodular ascaroside pasa#9 was discovered from the exo-metabolome of P. pacificus (Yim et al. 2015). Meanwhile, chemical analysis of the pheromone production in closely related Pristionchus species demonstrated intraspecific competition through cross preference of dauer pheromone (Bose et al. 2014).
To study small molecules modulated chemical communication between Pristionchus nematodes, comparative metabolomics based on MS and NMR (dqf-COSY) is applied in our laboratory. We use a precursor ion (m/z = 73) MS/MS screening method to profile ascarosides (and paratosides) from the exo-metabolome of Pristionchus species. Targeted small molecules with high interest are isolated or enriched via HPLC and structurally characterized with a combination of high resolution MS, two dimensional NMR and chemical synthesis. Their biochemical diversity, biosynthetic pathway as well as biological function will be further investigated. Additionally, we are investigating the crucial genes and enzymes involved in the biosynthesis of these signaling compounds from P. pacificus through analyzing chemical and genomic content of wild type isolates, hybrids and CRISPR generated mutants. Through biochemical analysis and working closely with many other evolutionary biologists and ecologists in our laboratory, we expect to uncover small molecules associated evolution and development in P. pacificus and provide a better understanding about the biosynthesis of these important signaling molecules.
Markov, G. V., Meyer, J. M., Panda, O., Artyukhin, A. B., Claaßen, M., Witte, H., Schroeder, F. C. & Sommer, R. J. (2016): Functional conservation and divergence of daf-22 paralogs in P. pacificus dauer development. Mol Biol Evol., 33, 2506-2514.
Yim, J., Bose, N., Meyer, J. M., Sommer, R. J. & Schroeder, F. C. (2015): Nematode signaling molecules derived from multimodular assembly of primary metabolic building blocks. Org. Lett., 17, 1648-1651.
Bose, N., Meyer, J. M., Yim, J. J., Mayer, M. G., Markov G. V., Ogawa, A., Schroeder, F. C., Sommer, R. J. (2014): Natural variation in dauer pheromone production and sensing supports intraspecific competition in nematodes. Current Biology, 24, 1536-1541.
Bose, N., Ogawa, A., von Reuss, S. H., Yim, J. J., Ragsdale, E. J., Sommer, R. J. & Schroeder, F. C. (2012): Complex small molecular architectures regulate phenotypic plasticity in a nematode. Angewandte Chemie, 51, 12438-12443.
Mayer, M. G. & Sommer R. J. (2011): Natural variation in Pristionchus pacificus dauer formation reveals cross-preference rather than self-preference of nematode dauer pheromones. Proc. R. Soc. B, 278, 2784-2790.
Bento, G., Ogawa, A. & Sommer, R. J. (2010): Co-option of the hormone-signalling module dafachronic acid–DAF-12 in nematode evolution. Nature, 466, 494-497.
Ogawa, A., Streit, A., Antebi, A. & Sommer R. J. (2009): A conserved endocrine mechanism controls the formation of dauer and infective larvae in nematodes. Current Biology, 19, 67-71.