화학공학소재연구정보센터
Journal of the American Chemical Society, Vol.141, No.5, 1842-1846, 2019
Thiopeptide Pyridine Synthase TbtD Catalyzes an Intermolecular Formal Aza-Diels-Alder Reaction
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.