Premium
Prerequisites of Isopeptide Bond Formation in Microcystin Biosynthesis
Author(s) -
Meyer Sabine,
Mainz Andi,
Kehr JanChristoph,
Süssmuth Roderich D.,
Dittmann Elke
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700389
Subject(s) - nonribosomal peptide , adenylylation , biosynthesis , chemistry , context (archaeology) , stereochemistry , peptide bond , biochemistry , amino acid , microcystin , biology , cyanobacteria , enzyme , bacteria , paleontology , genetics
Abstract The biosynthesis of the potent cyanobacterial hepatotoxin microcystin involves isopeptide bond formation through the carboxylic acid side chains of d ‐glutamate and β‐methyl d ‐aspartate. Analysis of the in vitro activation profiles of the two corresponding adenylation domains, McyE‐A and McyB‐A 2 , either in a didomain or a tridomain context with the cognate thiolation domain and the upstream condensation domain revealed that substrate activation of both domains strictly depended on the presence of the condensation domains. We further identified two key amino acids in the binding pockets of both adenylation domains that could serve as a bioinformatic signature of isopeptide bond‐forming modules incorporating d ‐glutamate or d ‐aspartate. Our findings further contribute to the understanding of the multifaceted role of condensation domains in nonribosomal peptide synthetase assembly lines.