ArticleNature communications2021
Mapping the biosynthetic pathway of a hybrid polyketide-nonribosomal peptide in a metazoan.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Stage-Specific carcinogenic mechanisms and intervention strategies for pksArchives of microbiology · 2026Review
- An Alkaloid Biosynthetic Gene Bundle in Animals.Journal of the American Chemical Society · 2026Article
- Stereoselective Synthesis and Antiproliferative Activity of Nemamide Analogs.Journal of natural products · 2025Article
- The Role of Nucleotide Sequencing in Natural Product Drug Discovery.Journal of natural products · 2025Review
- A widespread metabolic gene cluster family in metazoans.Nature chemical biology · 2025Article
- Characterizing the Biochemical Role of an Unusual Fatty Acyl-AMP Ligase from a Hybrid PKS-NRPS Pathway in Nematodes.ACS chemical biology · 2025Article
- Animal-Encoded Nonribosomal Pathway to Bursatellin Analogs.Journal of the American Chemical Society · 2025Article
- Discovery of a parallel family of euglenatide analogs in Euglena gracilis.Natural products and bioprospecting · 2025Article
- Comparative analysis of new mScarlet-based red fluorescent tags in Caenorhabditis elegans.Genetics · 2024Article
- Article
- Bdelloid rotifers deploy horizontally acquired biosynthetic genes against a fungal pathogen.Nature communications · 2024Article
- Comparative analysis of new, mScarlet-based red fluorescent tags inbioRxiv : the preprint server for biology · 2024Article
- Repurposing degradation pathways for modular metabolite biosynthesis in nematodes.Nature chemical biology · 2023Review
- Reactivity and mechanism in chemical and synthetic biology.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- A single amino acid residue controls acyltransferase activity in a polyketide synthase fromiScience · 2022Article
- Euglenatides, Potent Antiproliferative Cyclic Peptides Isolated from the Freshwater Photosynthetic Microalga Euglena gracilis.Angewandte Chemie (International ed. in English) · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) hybrid systems typically use complex protein-protein interactions to facilitate direct transfer of intermediates between these multimodular megaenzymes. In the canal-associated neurons (CANs) of Caenorhabditis elegans, PKS-1 and NRPS-1 produce the nemamides, the only known hybrid polyketide-nonribosomal peptides biosynthesized by animals, through a poorly understood mechanism. Here, we use genome editing and mass spectrometry to map the roles of individual PKS-1 and NRPS-1 enzymatic domains in nemamide biosynthesis. Furthermore, we show that nemamide biosynthesis requires at least five additional enzymes expressed in the CANs that are encoded by genes distributed across the worm genome. We identify the roles of these enzymes and discover a mechanism for trafficking intermediates between a PKS and an NRPS. Specifically, the enzyme PKAL-1 activates an advanced polyketide intermediate as an adenylate and directly loads it onto a carrier protein in NRPS-1. This trafficking mechanism provides a means by which a PKS-NRPS system can expand its biosynthetic potential and is likely important for the regulation of nemamide biosynthesis.
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