First, some background
Many bacteria and plants produce structurally complex chemical compounds for communication and regulation, including polyketides and nonribosomal peptides. Because such organic substances have the potential to be synthesized and developed into products used in medicines and pest control, they are of great interest to scientists.
What did the scientists discover?
Scientists extracted minute amounts of a substance from Caenorhabditis elegans (or C. elegans), a 1-mm long roundworm (or nematode), and used nuclear magnetic resonance (NMR) to study its composition and stereochemistry (exactly how the atoms are arranged three-dimensionally). They learned that the compound, produced by enzymes in two of the worm’s neurons, is a special kind of hybrid peptide that combines a polyketide with a nonribosomal peptide. Dubbed a "nemamide," this complex compound is fairly unusual for its hybrid nature, and quite unusual for having been found in an animal, rather than a plant or microorganism.
Why is this important?
Polyketides and nonribosomal peptides have been developed into many important therapeutics. Until now, most of those therapeutics have been derived from plant materials. With this discovery, scientists believe they have tapped into a vast new source of potential pharmaceuticals and other useful chemicals. That is because the enzymes that produce the nemamides in C. elegans (which are believed to protect the larvae from starvation) are also found in many other nematode species. Nematodes are numerous, ubiquitous and varied (the number of species has been estimated at about 1 million), making the amount of potential new compounds awaiting discovery mind-boggling.
Having discovered the chemical structure of this nemamide, scientists will now be able to synthesize larger quantities of it, enabling further study of the intriguing compound. Scientists may also discover further compounds that could help control the large percentage of nematodes that are parasitic, in addition to possible pharmaceutical applications.
Who did the research?
Shou, Q., Feng, L., Long, Y., Han, J., Nunnery, J.K., Powell, D.H., Butcher, R.A.,
University of Florida
Why did they need the MagLab?
Only very minute quantities of the nemamides could be purified from C. elegans. Thus, the ultra-sensitive, high-temperature superconducting NMR probe at the MagLab was required to solve the structure of the nemamides. NMR is the only technique that could discern both the chemical composition and the stereochemistry of these complex compounds.
Details for scientists
- View or download the expert-level Science Highlight, A hybrid peptide in nematodes that promotes larval survival
- Read the full-length publication, A hybrid polyketide-nonribosomal peptide that promotes larval survival, in Nat. Chem. Biol.
This research was funded by the following grants: G.S. Boebinger (NSF DMR-1157490); R.A. Butcher (NSF, Career 1555050; NIH, GM118775; Ellison Medical Foundation, AG-NS-0963-12; Alfred P. Sloan Foundation, BR2014-071)
For more information, contact Joanna Long.