Structural insights into enzymatic [4+2] aza-cycloaddition in thiopeptide antibiotic biosynthesis.

ABSTRACT: The [4+2] cycloaddition reaction is an enabling transformation in modern synthetic organic chemistry, but there are only limited examples of dedicated natural enzymes that can catalyze this transformation. Thiopeptides (or more formally thiazolyl peptides) are a class of thiazole-containing, highly modified, macrocyclic secondary metabolites made from ribosomally synthesized precursor peptides. The characteristic feature of these natural products is a six-membered nitrogenous heterocycle that is assembled via a formal [4+2] cycloaddition between two dehydroalanine (Dha) residues. This heteroannulation is entirely contingent on enzyme activity, although the mechanism of the requisite pyridine/dehydropiperidine synthase remains to be elucidated. The unusual aza-cylic product is distin

SUBMITTER: Cogan DP 

PROVIDER: S-EPMC5724283 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature