Phosphorylation of peptides by a kinase domain in cyanobactin pathways.
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| Format: | Artículo científico |
| Sprache: | en |
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Nature communications
2025
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| author | Castelo-Branco, Raquel Ouyang, Xiaodan Reis, João P A Freitas, Sara Sousa, Diana Fewer, David P Leão, Pedro N |
| author_facet | Castelo-Branco, Raquel Ouyang, Xiaodan Reis, João P A Freitas, Sara Sousa, Diana Fewer, David P Leão, Pedro N Castelo-Branco, Raquel Ouyang, Xiaodan Reis, João P A Freitas, Sara Sousa, Diana Fewer, David P Leão, Pedro N |
| collection | PubMed - marine biology |
| contents | Phosphorylation of peptides by a kinase domain in cyanobactin pathways. Castelo-Branco, Raquel Ouyang, Xiaodan Reis, João P A Freitas, Sara Sousa, Diana Fewer, David P Leão, Pedro N Phosphorylation Protein Processing, Post-Translational Peptides, Cyclic Bacterial Proteins Multigene Family Protein Domains Peptides Cyanobacteria Protein Kinases Mutagenesis, Site-Directed Phosphorylation is an important protein post-translational modification and a valuable tool in medicinal chemistry for improving the pharmacological properties of small molecules, but rare in natural product biosynthesis. Here we report phosphorylation in cyanobactins, a family of ribosomally synthesized and post-translationally modified peptides. We identify an unusual kinase domain embedded in the C-terminal macrocyclase encoded in cyanobactin biosynthetic gene clusters and link it to the production of phosphorylated dolichospermamides and aphanizomenamides. Heterologous expression, domain deletion and site directed mutagenesis confirm the role of the kinase domain, while transplantation of this domain into the sphaerocyclamide pathway leads to the production of phosphorylated sphaerocyclamides. The kinase domain acts on both linear and cyclic substrates with preference for Tyr residues. Collectively, these findings expand the diversity of post-translational modifications in cyanobactins and establish a versatile strategy for the engineering and combinatorial biosynthesis of phosphorylated peptides. |
| format | Artículo científico |
| id | pubmed_41271676 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Nature communications |
| record_format | pubmed |
| spellingShingle | Phosphorylation of peptides by a kinase domain in cyanobactin pathways. Castelo-Branco, Raquel Ouyang, Xiaodan Reis, João P A Freitas, Sara Sousa, Diana Fewer, David P Leão, Pedro N Phosphorylation Protein Processing, Post-Translational Peptides, Cyclic Bacterial Proteins Multigene Family Protein Domains Peptides Cyanobacteria Protein Kinases Mutagenesis, Site-Directed Phosphorylation of peptides by a kinase domain in cyanobactin pathways. Castelo-Branco, Raquel Ouyang, Xiaodan Reis, João P A Freitas, Sara Sousa, Diana Fewer, David P Leão, Pedro N Phosphorylation Protein Processing, Post-Translational Peptides, Cyclic Bacterial Proteins Multigene Family Protein Domains Peptides Cyanobacteria Protein Kinases Mutagenesis, Site-Directed Phosphorylation is an important protein post-translational modification and a valuable tool in medicinal chemistry for improving the pharmacological properties of small molecules, but rare in natural product biosynthesis. Here we report phosphorylation in cyanobactins, a family of ribosomally synthesized and post-translationally modified peptides. We identify an unusual kinase domain embedded in the C-terminal macrocyclase encoded in cyanobactin biosynthetic gene clusters and link it to the production of phosphorylated dolichospermamides and aphanizomenamides. Heterologous expression, domain deletion and site directed mutagenesis confirm the role of the kinase domain, while transplantation of this domain into the sphaerocyclamide pathway leads to the production of phosphorylated sphaerocyclamides. The kinase domain acts on both linear and cyclic substrates with preference for Tyr residues. Collectively, these findings expand the diversity of post-translational modifications in cyanobactins and establish a versatile strategy for the engineering and combinatorial biosynthesis of phosphorylated peptides. |
| title | Phosphorylation of peptides by a kinase domain in cyanobactin pathways. |
| topic | Phosphorylation Protein Processing, Post-Translational Peptides, Cyclic Bacterial Proteins Multigene Family Protein Domains Peptides Cyanobacteria Protein Kinases Mutagenesis, Site-Directed |
| url | https://pubmed.ncbi.nlm.nih.gov/41271676/ |