Unprecedented Noncanonical Features of the Nonlinear Nonribosomal Peptide Synthetase Assembly Line for WS9326A Biosynthesis
| Autor: | Myoun‐Su Kim, Munhyung Bae, Ye‐Eun Jung, Jung Min Kim, Sunghoon Hwang, Myoung Chong Song, Yeon Hee Ban, Eun Seo Bae, Suckchang Hong, Sang Kook Lee, Sun‐Shin Cha, Dong‐Chan Oh, Yeo Joon Yoon |
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| Rok vydání: | 2021 |
| Předmět: |
chemistry.chemical_classification
biology Molecular Structure 010405 organic chemistry Stereochemistry General Medicine General Chemistry 010402 general chemistry biology.organism_classification 01 natural sciences Streptomyces Affinities Catalysis 0104 chemical sciences Amino acid chemistry.chemical_compound Enzyme Thioesterase Biosynthesis chemistry Nonribosomal peptide Depsipeptides Peptide Synthases Adenylylation |
| Zdroj: | Angewandte Chemie (International ed. in English). 60(36) |
| ISSN: | 1521-3773 |
| Popis: | Systematic inactivation of nonribosomal peptide synthetase (NRPS) domains and translocation of the thioesterase (TE) domain revealed several unprecedented nonlinear NRPS assembly processes during the biosynthesis of the cyclodepsipeptide WS9326A in Streptomyces sp. SNM55. First, two sets of type ΙΙ TE (TEΙΙ)-like enzymes mediate the shuttling of activated amino acids between two sets of stand-alone adenylation (A)-thiolation (T) didomain modules and an 'A-less' condensation (C)-T module with distinctive specificities and flexibilities. This was confirmed by the elucidation of the affinities of the A-T didomains for the TEΙΙs and its structure. Second, the C-T didomain module operates iteratively and independently from other modules in the same protein to catalyze two chain elongation cycles. Third, this biosynthetic pathway includes the first example of module skipping, where the interpolated C and T domains are required for chain transfer. Understanding such untapped nonlinear biosynthetic strategies will provide potentially valuable tools for engineered biosynthesis of these complex natural products. |
| Databáze: | OpenAIRE |
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