Pattern-Based Genome Mining Guides Discovery of the Antibiotic Indanopyrrole A from a Marine Streptomycete.
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| Main Authors: | , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
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Journal of natural products
2024
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| _version_ | 1868266277677563905 |
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| author | Sweeney, Douglas Bogdanov, Alexander Chase, Alexander B Castro-Falcón, Gabriel Trinidad-Javier, Alma Dahesh, Samira Nizet, Victor Jensen, Paul R |
| author_facet | Sweeney, Douglas Bogdanov, Alexander Chase, Alexander B Castro-Falcón, Gabriel Trinidad-Javier, Alma Dahesh, Samira Nizet, Victor Jensen, Paul R Sweeney, Douglas Bogdanov, Alexander Chase, Alexander B Castro-Falcón, Gabriel Trinidad-Javier, Alma Dahesh, Samira Nizet, Victor Jensen, Paul R |
| collection | PubMed - marine biology |
| contents | Pattern-Based Genome Mining Guides Discovery of the Antibiotic Indanopyrrole A from a Marine Streptomycete. Sweeney, Douglas Bogdanov, Alexander Chase, Alexander B Castro-Falcón, Gabriel Trinidad-Javier, Alma Dahesh, Samira Nizet, Victor Jensen, Paul R Streptomyces Anti-Bacterial Agents Molecular Structure Multigene Family Pyrroles Biological Products Marine Biology Genome, Bacterial Terrestrial actinomycetes in the genus have long been recognized as prolific producers of small-molecule natural products, including many clinically important antibiotics and cytotoxic agents. Although can also be isolated from marine environments, their potential for natural product biosynthesis remains underexplored. The MAR4 clade of largely marine-derived has been a rich source of novel halogenated natural products of diverse structural classes. To further explore the biosynthetic potential of this group, we applied pattern-based genome mining, leading to the discovery of the first halogenated pyrroloketoindane natural products, indanopyrrole A () and B (), and the bioinformatic linkage of these compounds to an orphan biosynthetic gene cluster (BCG) in 20 MAR4 genomes. Indanopyrrole A displays potent broad-spectrum antibiotic activity against clinically relevant pathogens. A comparison of the putative indanopyrrole BGC with that of the related compound indanomycin provides new insights into the terminal cyclization and offloading mechanisms in pyrroloketoindane biosynthesis. Broader searches of public databases reveal the rarity of this BGC while also highlighting opportunities for discovering additional compounds in this uncommon class. |
| format | Artículo científico |
| id | pubmed_39575834 |
| institution | PubMed |
| language | en |
| publishDate | 2024 |
| publisher | Journal of natural products |
| record_format | pubmed |
| spellingShingle | Pattern-Based Genome Mining Guides Discovery of the Antibiotic Indanopyrrole A from a Marine Streptomycete. Sweeney, Douglas Bogdanov, Alexander Chase, Alexander B Castro-Falcón, Gabriel Trinidad-Javier, Alma Dahesh, Samira Nizet, Victor Jensen, Paul R Streptomyces Anti-Bacterial Agents Molecular Structure Multigene Family Pyrroles Biological Products Marine Biology Genome, Bacterial Pattern-Based Genome Mining Guides Discovery of the Antibiotic Indanopyrrole A from a Marine Streptomycete. Sweeney, Douglas Bogdanov, Alexander Chase, Alexander B Castro-Falcón, Gabriel Trinidad-Javier, Alma Dahesh, Samira Nizet, Victor Jensen, Paul R Streptomyces Anti-Bacterial Agents Molecular Structure Multigene Family Pyrroles Biological Products Marine Biology Genome, Bacterial Terrestrial actinomycetes in the genus have long been recognized as prolific producers of small-molecule natural products, including many clinically important antibiotics and cytotoxic agents. Although can also be isolated from marine environments, their potential for natural product biosynthesis remains underexplored. The MAR4 clade of largely marine-derived has been a rich source of novel halogenated natural products of diverse structural classes. To further explore the biosynthetic potential of this group, we applied pattern-based genome mining, leading to the discovery of the first halogenated pyrroloketoindane natural products, indanopyrrole A () and B (), and the bioinformatic linkage of these compounds to an orphan biosynthetic gene cluster (BCG) in 20 MAR4 genomes. Indanopyrrole A displays potent broad-spectrum antibiotic activity against clinically relevant pathogens. A comparison of the putative indanopyrrole BGC with that of the related compound indanomycin provides new insights into the terminal cyclization and offloading mechanisms in pyrroloketoindane biosynthesis. Broader searches of public databases reveal the rarity of this BGC while also highlighting opportunities for discovering additional compounds in this uncommon class. |
| title | Pattern-Based Genome Mining Guides Discovery of the Antibiotic Indanopyrrole A from a Marine Streptomycete. |
| topic | Streptomyces Anti-Bacterial Agents Molecular Structure Multigene Family Pyrroles Biological Products Marine Biology Genome, Bacterial |
| url | https://pubmed.ncbi.nlm.nih.gov/39575834/ |