ArticleNature chemical biology2018
Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme.
Article in Nature chemical biology, 2018. 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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14 citing papers in PubMed, 23 citations in OpenAlex.
- Evolutionary engineering of Geobacillus thermoleovorans for growth on adipic acid and 1,4-butanediol.Applied microbiology and biotechnology · 2026Article
- Coenzyme A Tethering Mediates Dehydratase Substrate Promiscuity and Reaction Specificity in Platensimycin, Platencin, and Platensilin Biosynthesis.Biochemistry · 2025Article
- Enzymatic synthesis of azide by a promiscuous N-nitrosylase.Nature chemistry · 2024Article
- Development of platensimycin, platencin, and platensilin overproducers by biosynthetic pathway engineering and fermentation medium optimization.Journal of industrial microbiology & biotechnology · 2024Article
- Rapid Biocatalytic Synthesis of Aromatic Acid CoA Thioesters by Using Microbial Aromatic Acid CoA Ligases.Chembiochem : a European journal of chemical biology · 2023Article
- Mapping the biosynthetic pathway of a hybrid polyketide-nonribosomal peptide in a metazoan.Nature communications · 2021Article
- Bacterial terpenome.Natural product reports · 2021Review
- PtmC Catalyzes the Final Step of Thioplatensimycin, Thioplatencin, and Thioplatensilin Biosynthesis and Expands the Scope of ArylamineACS chemical biology · 2021Article
- Global analysis of adenylate-forming enzymes reveals β-lactone biosynthesis pathway in pathogenicThe Journal of biological chemistry · 2020Article
- The Biosynthesis of the Benzoxazole in Nataxazole Proceeds via an Unstable Ester and has Synthetic Utility.Angewandte Chemie (International ed. in English) · 2020Article
- Characterization and Crystal Structure of a Nonheme Diiron Monooxygenase Involved in Platensimycin and Platencin Biosynthesis.Journal of the American Chemical Society · 2019Article
- Targeting adenylate-forming enzymes with designed sulfonyladenosine inhibitors.The Journal of antibiotics · 2019Review
- Cryptic and Stereospecific Hydroxylation, Oxidation, and Reduction in Platensimycin and Platencin Biosynthesis.Journal of the American Chemical Society · 2019Article
- Structural genomics and the Protein Data Bank.The Journal of biological chemistryReview
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11 authors at 3 institutions in 1 country.
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Abstract
Acyl-coenzyme A (CoA) ligases catalyze the activation of carboxylic acids via a two-step reaction of adenylation followed by thioesterification. Here, we report the discovery of a non-adenylating acyl-CoA ligase PtmA2 and the functional separation of an acyl-CoA ligase reaction. Both PtmA1 and PtmA2, two acyl-CoA ligases from the biosynthetic pathway of platensimycin and platencin, are necessary for the two steps of CoA activation. Gene inactivation of ptmA1 and ptmA2 resulted in the accumulation of free acid and adenylate intermediates, respectively. Enzymatic and structural characterization of PtmA2 confirmed its ability to only catalyze thioesterification. Structural characterization of PtmA2 revealed it binds both free acid and adenylate substrates and undergoes the established mechanism of domain alternation. Finally, site-directed mutagenesis restored both the adenylation and complete CoA activation reactions. This study challenges the currently accepted paradigm of adenylating enzymes and inspires future investigations on functionally separated acyl-CoA ligases and their ramifications in biology.
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