A multifunctional PKS-NRPS megasynthetase in nematodes produces divergent signaling molecules that control different developmental arrests.
- 1Department of Chemistry, University of Florida, Gainesville, FL, USA.
- 2Department for Integrative Evolutionary Biology, Max Planck Institute for Biology, Tübingen, Tübingen, Germany.
- 3Department of Chemistry, University of Florida, Gainesville, FL, USA. [email protected].
Abstract
To maximize their reproductive success, nematodes not only must arrest their development in response to adverse growth conditions but also must quickly recover if conditions improve. However, the molecular signals that coordinate these transitions remain poorly understood. Here, we show that a hybrid polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) expressed in the canal-associated neurons (CANs) is a central regulator of multiple developmental arrest programs, including starvation-induced larval arrest and dauer development. Using unbiased, comparative metabolomics in the predatory nematode Pristionchus pacificus, we show that this PKS-NRPS assembly line produces a suite of secondary metabolites, including a family of hybrid polyketide-nonribosomal peptides known as the nemamides, the related nemaketides, and a family of ascarylose-modified polyketides that we term ascarenes. Depending on the starter unit that is loaded onto the assembly line, the PKS-NRPS megasynthetase can produce dramatically different downstream products. Genetic analysis of the assembly line suggests that the nemamides promote recovery from starvation-induced larval arrest, while the ascarenes inhibit dauer development. Our work demonstrates that the PKS-NRPS assembly line serves as a signaling hub in the CANs, producing multiple signaling molecules that control different developmental events.
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BibTeX
@article{mai2026multifunctional,
title = {{A multifunctional PKS-NRPS megasynthetase in nematodes produces divergent signaling molecules that control different developmental arrests.}},
author = {Kevin Mai and Chi-Su Yoon and Dilip V Prajapati and Yuelan Li and Rongrong Yu and Hanh Witte and Subhradeep Bhar and Likui Feng and David A deGuzman and Elijah Abraham and Matthew T Gordon and Surasree Rakshit and Melisa S Gonzalez and Priya and Ralf J Sommer and Rebecca A Butcher},
journal = {Nature communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77265-x},
url = {https://europepmc.org/article/MED/42901919},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A multifunctional PKS-NRPS megasynthetase in nematodes produces divergent signaling molecules that control different developmental arrests.
AU - Kevin Mai
AU - Chi-Su Yoon
AU - Dilip V Prajapati
AU - Yuelan Li
AU - Rongrong Yu
AU - Hanh Witte
AU - Subhradeep Bhar
AU - Likui Feng
AU - David A deGuzman
AU - Elijah Abraham
AU - Matthew T Gordon
AU - Surasree Rakshit
AU - Melisa S Gonzalez
AU - Priya
AU - Ralf J Sommer
AU - Rebecca A Butcher
PY - 2026
DA - 2026/09/29
JO - Nature communications
DO - 10.1038/s41467-026-77265-x
UR - https://europepmc.org/article/MED/42901919
AB - To maximize their reproductive success, nematodes not only must arrest their development in response to adverse growth conditions but also must quickly recover if conditions improve. However, the molecular signals that coordinate these transitions remain poorly understood. Here, we show that a hybrid polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) expressed in the canal-associated neurons (CANs) is a central regulator of multiple developmental arrest programs, including starvation-induced larval arrest and dauer development. Using unbiased, comparative metabolomics in the predatory nematode Pristionchus pacificus, we show that this PKS-NRPS assembly line produces a suite of secondary metabolites, including a family of hybrid polyketide-nonribosomal peptides known as the nemamides, the related nemaketides, and a family of ascarylose-modified polyketides that we term ascarenes. Depending on the starter unit that is loaded onto the assembly line, the PKS-NRPS megasynthetase can produce dramatically different downstream products. Genetic analysis of the assembly line suggests that the nemamides promote recovery from starvation-induced larval arrest, while the ascarenes inhibit dauer development. Our work demonstrates that the PKS-NRPS assembly line serves as a signaling hub in the CANs, producing multiple signaling molecules that control different developmental events.
SN - 2041-1723
ER -