ArticleAngewandte Chemie (International ed. in English)2015
Enzymatic basis of "hybridity" in thiomarinol biosynthesis.
Article in Angewandte Chemie (International ed. in English), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 36 citations in OpenAlex.
- Design, Synthesis, and Antitubercular Activity of Thiolutin-Cycloserine Hybrids: Reducing Cytotoxicity.Microorganisms · 2026Article
- Mutasynthesis and Antibiotic Activity of Mupirocin Analogues.Chembiochem : a European journal of chemical biology · 2026Article
- The Hybrid Antibiotic Thiomarinol A Overcomes Intrinsic Resistance inACS infectious diseases · 2024Article
- A Cysteine-Reloading Process Initiating the Biosynthesis of the Bicyclic Scaffold of Dithiolopyrrolones.Antibiotics (Basel, Switzerland) · 2023Article
- Chemical Evolution of Natural Product Structure.Journal of the American Chemical Society · 2022Article
- Inhibition of Isoleucyl-tRNA Synthetase by the Hybrid Antibiotic Thiomarinol.Journal of the American Chemical Society · 2021Article
- Genome Mining of Oxidation Modules in trans-Acyltransferase Polyketide Synthases Reveals a Culturable Source for Lobatamides.Angewandte Chemie (International ed. in English) · 2020Article
- Biocatalytic Synthesis of Moclobemide Using the Amide Bond Synthetase McbA Coupled with an ATP Recycling System.ACS catalysis · 2020Article
- The Isolation of Pyrroloformamide Congeners and Characterization of Their Biosynthetic Gene Cluster.Journal of natural products · 2020Article
- Crossroads of Antibiotic Resistance and Biosynthesis.Journal of molecular biology · 2019Review
- Culturing marine bacteria from the genus Pseudoalteromonas on a cotton scaffold alters secondary metabolite production.MicrobiologyOpen · 2019Article
- Defining the genes for the final steps in biosynthesis of the complex polyketide antibiotic mupirocin by Pseudomonas fluorescens NCIMB10586.Scientific reports · 2019Article
- Investigating the Biosynthesis of Natural Products from Marine Proteobacteria: A Survey of Molecules and Strategies.Marine drugs · 2017Review
- Role for dithiolopyrrolones in disrupting bacterial metal homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Thiomarinol is a naturally occurring double-headed antibiotic that is highly potent against methicillin-resistant Staphylococcus aureus. Its structure comprises two antimicrobial subcomponents, pseudomonic acid analogue and holothin, linked by an amide bond. TmlU was thought to be the sole enzyme responsible for this amide-bond formation. In contrast to this idea, we show that TmlU acts as a CoA ligase that activates pseudomonic acid as a thioester that is processed by the acetyltransferase HolE to catalyze the amidation. TmlU prefers complex acyl acids as substrates, whereas HolE is relatively promiscuous, accepting a range of acyl-CoA and amine substrates. Our results provide detailed biochemical information on thiomarinol biosynthesis, and evolutionary insight regarding how the pseudomonic acid and holothin pathways converge to generate this potent hybrid antibiotic. This work also demonstrates the potential of TmlU/HolE enzymes as engineering tools to generate new "hybrid" molecules.
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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 OpenQuestion graph.