Premium
Role of Two Exceptional trans Adenylation Domains and MbtH‐like Proteins in the Biosynthesis of the Nonribosomal Peptide WS9324A from Streptomyces calvus ATCC 13382
Author(s) -
Bernhardt Mirjam,
Berman Stefanie,
Zechel David,
Bechthold Andreas
Publication year - 2020
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.202000142
Subject(s) - adenylylation , nonribosomal peptide , biosynthesis , biology , amino acid , gene cluster , peptide , biochemistry , gene
Nonribosomal peptide synthetases (NRPS) are organized in a modular arrangement. Usually, the modular order corresponds to the assembly of the amino acids in the respective peptide, following the collinearity rule. The WS9326A biosynthetic gene cluster from Streptomyces calvus shows deviations from this rule. Most interesting is the presence of two trans adenylation domains that are located downstream of the modular NRPS arrangement. Adenylation domains are responsible for the activation of their respective amino acids. In this study, we confirmed the involvement of the trans adenylation domains in WS9326A biosynthesis by performing gene knockout experiments and by observing the selective adenylation of their predicted amino acid substrates in vitro . We conclude that the trans adenylation domains are essential for WS9326A biosynthesis. Moreover, both adenylation domains are observed to have MbtH‐like protein dependency. Overall, we conclude that the trans adenylation domains are essential for WS9326A biosynthesis.