ArticleNature communications2021
Thioesterase-mediated side chain transesterification generates potent Gq signaling inhibitor FR900359.
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 26 papers.
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Who cites it
26 citing papers in PubMed.
- Multi-Targeting Non-Specific Genome Engineering in Bacteria.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protease-Activated Receptor 1 as an Endogenous Model of Peptidergic Gαq-Gα12-Biased G Protein Signaling.bioRxiv : the preprint server for biology · 2026Article
- Covalent warhead assembly in fostriecin biosynthesis involves malonylation-lactonisation by a bifunctional thioesterase and enzymatic demalonylation.Nature communications · 2026Article
- Pseudotetraivprolides from Pseudomonas entomophila Provide Insights into the Biosynthesis of Detoxin/Rimosamide-Like Anti-Antibiotics.Angewandte Chemie (International ed. in English) · 2026Article
- Protease-activated receptor 1 as an endogenous model of peptidergic Gαq-Gα12-biased G protein signaling.Frontiers in molecular biosciences · 2026Article
- Identification of strong constitutive promoters in Burkholderia stagnalis TBRC 18363 for activating natural product production in Gram-negative bacteria.Applied microbiology and biotechnology · 2025Article
- Non-canonical thioesterases in bacterial non-ribosomal peptide biosynthesis.The Journal of antibiotics · 2025Review
- GαScience signaling · 2025Article
- The thiazolidinedione drug troglitazone inhibits Gq signaling through direct binding to the Gq alpha subunit through inhibition of GDP release.Molecular pharmacology · 2025Article
- Cyclic peptide inhibitors function as molecular glues to stabilize Gq/11 heterotrimers.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structural response of G protein binding to the cyclodepsipeptide inhibitor FR900359 probed by NMR spectroscopy.Chemical science · 2024Article
- Plant peptides - redefining an area of ribosomally synthesized and post-translationally modified peptides.Natural product reports · 2024Review
- Dehydroamino acid residues in bioactive natural products.Natural product reports · 2024Review
- Recommended Tool Compounds: Application of YM-254890 and FR900359 to Interrogate GαACS pharmacology & translational science · 2023Review
- The Bacterial GJournal of chemical ecology · 2023Article
- Article
- Building Chemical Probes Based on the Natural Products YM-254890 and FR900359: Advances toward Scalability.Synthesis · 2023Article
- Cleavage Off-Loading and Post-assembly-Line Conversions Yield Products with Unusual Termini during Biosynthesis.ACS chemical biology · 2022Article
- A Specialized Dehydrogenase Provides l-Phenyllactate for FR900359 Biosynthesis.Chembiochem : a European journal of chemical biology · 2022Article
- Nonribosomal Peptide Synthesis Definitely Working Out of the Rules.Microorganisms · 2022Review
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The potent and selective Gq protein inhibitor depsipeptide FR900359 (FR), originally discovered as the product of an uncultivable plant endosymbiont, is synthesized by a complex biosynthetic system comprising two nonribosomal peptide synthetase (NRPS) assembly lines. Here we characterize a cultivable bacterial FR producer, enabling detailed investigations into biosynthesis and attachment of the functionally important FR side chain. We reconstitute side chain assembly by the monomodular NRPS FrsA and the non-heme monooxygenase FrsH, and characterize intermolecular side chain transesterification to the final macrocyclic intermediate FR-Core, mediated by the FrsA thioesterase domain. We harness FrsA substrate promiscuity to generate FR analogs with altered side chains and demonstrate indispensability of the FR side chain for efficient Gq inhibition by comparative bioactivity, toxicity and docking studies. Finally, evolution of FR and side chain biosynthesis is discussed based on bioinformatics analyses. Side chain transesterification boosts potency and target affinity of selective Gq inhibitor natural products.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.