ArticleProceedings of the National Academy of Sciences of the United States of America2015
In vitro reconstitution of indolmycin biosynthesis reveals the molecular basis of oxazolinone assembly.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- An Insight into Rational Drug Design: The Development of In-House Azole Compounds with Antimicrobial Activity.Antibiotics (Basel, Switzerland) · 2024Review
- The catechol moiety of obafluorin is essential for antibacterial activity.RSC chemical biology · 2023Article
- An engineered biosynthetic-synthetic platform for production of halogenated indolmycin antibiotics.Chemical science · 2021Article
- AApplied and environmental microbiology · 2021Article
- Design and synthesis of novel spirooxindole-indenoquinoxaline derivatives as novel tryptophanyl-tRNA synthetase inhibitors.Molecular diversity · 2020Article
- Global analysis of adenylate-forming enzymes reveals β-lactone biosynthesis pathway in pathogenicThe Journal of biological chemistry · 2020Article
- ARTS 2.0: feature updates and expansion of the Antibiotic Resistant Target Seeker for comparative genome mining.Nucleic acids research · 2020Article
- Recent developments in self-resistance gene directed natural product discovery.Natural product reports · 2020Review
- Identification of the Antifungal Metabolite Chaetoglobosin P FromFrontiers in microbiology · 2020Article
- Antioxidant activity and antibacterial evaluation of new thiazolin-4-one derivatives as potential tryptophanyl-tRNA synthetase inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- Convergent biosynthetic transformations to a bacterial specialized metabolite.Nature chemical biology · 2019Article
- Comparison of Antibiotic Resistance Mechanisms in Antibiotic-Producing and Pathogenic Bacteria.Molecules (Basel, Switzerland) · 2019Review
- The hidden enzymology of bacterial natural product biosynthesis.Nature reviews. Chemistry · 2019Article
- Biosynthesis of antibiotic chuangxinmycin fromActa pharmaceutica Sinica. B · 2018Article
- Investigating the Biosynthesis of Natural Products from Marine Proteobacteria: A Survey of Molecules and Strategies.Marine drugs · 2017Review
- A four-gene operon inThe Journal of biological chemistry · 2017Article
- A pyridoxal phosphate-dependent enzyme that oxidizes an unactivated carbon-carbon bond.Nature chemical biology · 2016Article
- Production of the Bioactive Compounds Violacein and Indolmycin Is Conditional in aFrontiers in microbiology · 2016Article
- Article
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3 authors.
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Abstract
The bacterial tryptophanyl-tRNA synthetase inhibitor indolmycin features a unique oxazolinone heterocycle whose biogenetic origins have remained obscure for over 50 years. Here we identify and characterize the indolmycin biosynthetic pathway, using systematic in vivo gene inactivation, in vitro biochemical assays, and total enzymatic synthesis. Our work reveals that a phenylacetate-CoA ligase-like enzyme Ind3 catalyzes an unusual ATP-dependent condensation of indolmycenic acid and dehydroarginine, driving oxazolinone ring assembly. We find that Ind6, which also has chaperone-like properties, acts as a gatekeeper to direct the outcome of this reaction. With Ind6 present, the normal pathway ensues. Without Ind6, the pathway derails to an unusual shunt product. Our work reveals the complete pathway for indolmycin formation and sets the stage for using genetic and chemoenzymatic methods to generate indolmycin derivatives as potential therapeutic agents.
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