TY  - JOUR
A1  - Meyer, Sabine
A1  - Mainz, Andi
A1  - Kehr, Jan-Christoph
A1  - Suessmuth, Roderich
A1  - Dittmann, Elke
T1  - Prerequisites of Isopeptide Bond Formation in Microcystin Biosynthesis
JF  - ChemBioChem : a European journal of chemical biology
N2  - The biosynthesis of the potent cyanobacterial hepatotoxin microcystin involves isopeptide bond formation through the carboxylic acid side chains of d-glutamate and -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.
KW  - amino acids
KW  - biosynthesis
KW  - cyanobacteria
KW  - nonribosomal peptide
KW  - substrate specificity
Y1  - 2017
U6  - https://doi.org/10.1002/cbic.201700389
SN  - 1439-4227
SN  - 1439-7633
VL  - 18
SP  - 2376
EP  - 2379
PB  - Wiley-VCH
CY  - Weinheim
ER  -