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Updated: Jan 30, 2026

The Preparation and Properties of Thermo-reversibly Cross-linked Rubber Via Diels-Alder Chemistry
Published on: August 25, 2016
Thiopeptide Pyridine Synthase TbtD Catalyzes an Intermolecular Formal Aza-Diels-Alder Reaction
Jonathan W Bogart1, Albert A Bowers1
1Division of Chemical Biology and Medicinal Chemistry Eshelman School of Pharmacy, and Lineberger Comprehensive Cancer Center , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina 27514 , United States.
Abstract:
Thiopeptide pyridine synthases catalyze a multistep reaction involving a unique and nonspontaneous intramolecular aza-[4 + 2] cycloaddition between two dehydroalanines to forge a trisubstituted pyridine core. We discovered that the in vitro activity of pyridine synthases from the thiocillin and thiomuracin pathways are significantly enhanced by general base catalysis and that this broadly expands the enzymes substrate tolerance. Remarkably, TbtD is competent to perform an intermolecular cyclization in addition to its cognate intramolecular reaction, underscoring its versatility as a biocatalyst. These data provide evidence that pyridine synthases use a two-site substrate recognition model to engage and process their substrates.
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