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In Vitro Biosynthesis of the Nonproteinogenic Amino Acid Methoxyvinylglycine
Author(s) -
Patteson Jon B.,
Dunn Zachary D.,
Li Bo
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201713419
Subject(s) - biosynthesis , amino acid , dipeptide , stereochemistry , chemistry , decarboxylation , ether , peptide , enzyme , peptide biosynthesis , peptide synthesis , biochemistry , organic chemistry , gene , ribosome , catalysis , rna
Oxyvinylglycines are a family of nonproteinogenic amino acids featuring an essential vinyl ether conferring mechanism‐based inhibition of pyridoxal phosphate enzymes. The gene clusters for a few oxyvinylglycines are known, yet the biosynthetic origin of the vinyl ether is elusive. The in vitro biosynthesis of methoxyvinylglycine or l ‐2‐amino‐4‐methoxy‐ trans ‐3‐butenoic acid (AMB) is reported. It is shown that AMB is made from glutamate as an alanyl‐AMB dipeptide and the rationale is provided for the N‐term Ala. Using a chemical capture method, the order and timing of the modifications on non‐ribosomal peptide synthetase (NRPS)‐bound substrates was determined, including a cryptic hydroxylation of the Glu β‐carbon. Eliminating this hydroxy group likely generates a key α,β‐dehydroamino acid intermediate that facilitates decarboxylation. This work sheds light on vinyl ether biosynthesis and uncovers new NRPS chemistry.