Role of Two Exceptional trans Adenylation Domains and MbtH-like Proteins in the Biosynthesis of the Nonribosomal Peptide WS9324A from Streptomyces calvus ATCC 13382
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Authors
Bernhardt, Mirjam
Berman, Stefanie
Zechel, David
Bechthold, Andreas
Date
2020-04-25
Type
journal article
Language
en
Keyword
Adenylation domains , Biosynthesis , Mutagenesis , Nonribosomal peptide synthetases , WS9326A
Alternative Title
Abstract
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.
Description
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Citation
Bernhardt, M.; Berman, S.; Zechel, D.; Bechthold, A. Role of Two Exceptional Trans Adenylation Domains and MbtH‐like Proteins in the Biosynthesis of the Nonribosomal Peptide WS9324A from Streptomyces Calvus ATCC 13382. Chembiochem : a European journal of chemical biology 2020, 21 (18), 2659–2666. https://doi.org/10.1002/cbic.202000142.
Publisher
Chemistry Europe - European Chemical Societies Publishing