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05:15
Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Differentiating 5-thiooxazoles from oxazolone-coupled thioamides in RiPP natural products
Biorxiv : the Preprint Server for Biology
|June 22, 2026
Summary
Multinuclear nonheme iron-dependent oxidative enzymes (MNIOs) modify peptides. This study differentiates 5-thiooxazole modifications from similar oxazolone-coupled thioamides in RiPP natural products using chemical characterization.
Area of Science:
- Biochemistry
- Natural Product Chemistry
- Enzymology
Background:
- Multinuclear nonheme iron-dependent oxidative enzymes (MNIOs) catalyze cysteine modifications in ribosomally synthesized, post-translationally modified peptides (RiPPs).
- Distinguishing 5-thiooxazole moieties from oxazolone-coupled thioamides, another MNIO product, is challenging in RiPP natural products.
- The RiPP virulence factor oxazolin features six copper-binding heterocycles installed by an MNIO.
Purpose of the Study:
- To reassign the post-translational modifications in oxazolin.
- To establish a benchmark for differentiating 5-thiooxazoles from oxazolone-coupled thioamides.
- To provide clarity for identifying these modifications in newly discovered RiPPs.
Main Methods:
- Detailed comparative chemical characterization of oxazolin and methanobactin.
- Structural characterization of the modified peptides.
- Analysis of post-translational modifications (PTMs) catalyzed by MNIOs.
Main Results:
- The post-translational modifications in oxazolin were reassigned from oxazolones/thioamides to 5-thiooxazoles.
- Comparative analysis provided clear differentiation criteria between 5-thiooxazoles and oxazolone-coupled thioamides.
- Methanobactin was used as a reference for oxazolone-coupled thioamides.
Conclusions:
- The study establishes 5-thiooxazoles as the correct PTM in oxazolin.
- A benchmark is set for distinguishing between 5-thiooxazoles and oxazolone-coupled thioamides in RiPPs.
- This work aids in the accurate identification of diverse RiPP natural products.
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