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A hybrid polyketide–nonribosomal peptide in nematodes that promotes larval survival

Nature Chemical Biology volume 12, pages 770–772 (2016)Cite this article

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Abstract

Polyketides and nonribosomal peptides are two important types of natural products that are produced by many species of bacteria and fungi but are exceedingly rare in metazoans. Here, we elucidate the structure of a hybrid polyketide–nonribosomal peptide from Caenorhabditis elegans that is produced in the canal-associated neurons (CANs) and promotes survival during starvation-induced larval arrest. Our results uncover a novel mechanism by which animals respond to nutrient fluctuations to extend survival.

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Figure 1: Discovery and biosynthesis of the nemamides.
Figure 2: Site of expression and biological role of the nemamides.

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Acknowledgements

We thank A. Fire, A. Frand, N. Moghal and P. Sengupta for plasmids, J. Rocca for help with NMR acquisition, J. Johnson for MS–MS analysis, Y. Ding and Y. Zhang for help with Sybyl software, S. Hagan, G. Fanucci, and Z. Liu for help with CD spectroscopy, and Y. Zhu for help with calculating CD spectra. We acknowledge the CGC, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440), and the NemaGENETAG consortium for providing strains. This work was supported by funds to R.A.B. from the NIH (GM118775), the NSF (1555050), the Ellison Medical Foundation (AG-NS-0963-12), the Alfred P. Sloan Foundation (BR2014-071), and the National High Magnetic Field Laboratory, which is supported by NSF Cooperative Agreement No. DMR-1157490 and the State of Florida.

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Author notes

  1. Qingyao Shou and Likui Feng: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Chemistry, University of Florida, Gainesville, Florida, USA

    Qingyao Shou, Likui Feng, Yaoling Long, Jungsoo Han, Joshawna K Nunnery, David H Powell & Rebecca A Butcher

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  1. Qingyao Shou
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  2. Likui Feng
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Contributions

Q.S. purified and structurally characterized the nemamides. L.F. generated transgenic worm strains and performed biological assays. Y.L. performed metabolomic analyses. J.H. generated extracts. J.K.N. analyzed nemamide stability. Q.S., L.F., Y.L., D.H.P., and R.A.B. analyzed the data. R.A.B., Q.S., and L.F. wrote the manuscript.

Corresponding author

Correspondence to Rebecca A Butcher.

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The authors declare no competing financial interests.

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Supplementary Results, Supplementary Figures 1–28 and Supplementary Tables 1–5 (PDF 8971 kb)

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Shou, Q., Feng, L., Long, Y. et al. A hybrid polyketide–nonribosomal peptide in nematodes that promotes larval survival. Nat Chem Biol 12, 770–772 (2016). https://doi.org/10.1038/nchembio.2144

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