ArticleProceedings of the National Academy of Sciences of the United States of America2016
Capture of micrococcin biosynthetic intermediates reveals C-terminal processing as an obligatory step for in vivo maturation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- Micrococcins from Peribacillus sp. KDM594; efficacy against vancomycin-resistant enterococci and drug metabolism in a silkworm model.The Journal of antibiotics · 2025Article
- Biosynthesis of peptide-nucleobase hybrids in ribosomal peptides.Nature chemical biology · 2025Article
- Discovery and Biosynthesis of Persiathiacins: Unusual Polyglycosylated Thiopeptides Active Against Multidrug Resistant Tuberculosis.ACS infectious diseases · 2024Article
- Decarboxylation in Natural Products Biosynthesis.JACS Au · 2024Review
- Micrococcin cysteine-to-thiazole conversion through transient interactions between the scaffolding protein TclI and the modification enzymes TclJ and TclN.Applied and environmental microbiology · 2024Article
- Genome-Based Characterization of a Plasmid-Associated Micrococcin P1 Biosynthetic Gene Cluster and Virulence Factors in Mammaliicoccus sciuri IMDO-S72.Applied and environmental microbiology · 2022Article
- A biosynthetic pathway to aromatic amines that uses glycyl-tRNA as nitrogen donor.Nature chemistry · 2022Article
- Thiocysteine lyases as polyketide synthase domains installing hydropersulfide into natural products and a hydropersulfide methyltransferase.Nature communications · 2021Article
- New developments in RiPP discovery, enzymology and engineering.Natural product reports · 2021Review
- Flexizyme-Enabled Benchtop Biosynthesis of Thiopeptides.Journal of the American Chemical Society · 2019Article
- Biosynthesis of the nosiheptide indole side ring centers on a cryptic carrier protein NosJ.Nature communications · 2017Article
- Elucidating and engineering thiopeptide biosynthesis.World journal of microbiology & biotechnology · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Thiopeptides, including micrococcins, are a growing family of bioactive natural products that are ribosomally synthesized and heavily modified. Here we use a refactored, modular in vivo system containing the micrococcin P1 (MP1) biosynthetic genes (TclIJKLMNPS) from Macrococcus caseolyticus str 115 in a genetically tractable Bacillus subtilis strain to parse the processing steps of this pathway. By fusing the micrococcin precursor peptide to an affinity tag and coupling it with catalytically defective enzymes, biosynthetic intermediates were easily captured for analysis. We found that two major phases of molecular maturation are separated by a key C-terminal processing step. Phase-I conversion of six Cys residues to thiazoles (TclIJN) is followed by C-terminal oxidative decarboxylation (TclP). This TclP-mediated oxidative decarboxylation is a required step for the peptide to progress to phase II. In phase II, Ser/Thr dehydration (TclKL) and peptide macrocycle formation (TclM) occurs. A C-terminal reductase, TclS, can optionally act on the substrate peptide, yielding MP1, and is shown to act late in the pathway. This comprehensive characterization of the MP1 pathway prepares the way for future engineering efforts.
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