Molecular basis for the biosynthesis of the siderophore coprogen in the cheese-ripening fungus Penicillium roqueforti
Abstract Background Iron is an essential nutrient for microorganisms, including fungi, which have evolved strategies to acquire it. The most common strategy is the secretion of siderophores, low-molecular-weight compounds with a high affinity for ferric ions, which are involved in cellular iron upta...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
|
| Series: | Biological Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40659-025-00633-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849767504989126656 |
|---|---|
| author | Kathia González Mariana Montanares Matías Gallardo Carlos Gil-Durán Abel M. Forero Jaime Rodríguez Carlos Jiménez Inmaculada Vaca Renato Chávez |
| author_facet | Kathia González Mariana Montanares Matías Gallardo Carlos Gil-Durán Abel M. Forero Jaime Rodríguez Carlos Jiménez Inmaculada Vaca Renato Chávez |
| author_sort | Kathia González |
| collection | DOAJ |
| description | Abstract Background Iron is an essential nutrient for microorganisms, including fungi, which have evolved strategies to acquire it. The most common strategy is the secretion of siderophores, low-molecular-weight compounds with a high affinity for ferric ions, which are involved in cellular iron uptake. Penicillium roqueforti, the fungus responsible for the ripening of blue-veined cheeses, produces coprogen, a hydroxamate-type siderophore. However, to date, the molecular basis for its biosynthesis remains elusive. Results In this study, we identified and characterized a biosynthetic gene cluster (BGC) responsible for coprogen biosynthesis in P. roqueforti, named the cop BGC. This BGC contains seven genes, three of which (copA, copB and copE) encode enzymes directly involved in coprogen biosynthesis from precursors molecules. Using CRISPR-Cas9, we targeted these three genes and analyzed the resulting mutants by Liquid Chromatography/High-Resolution Mass Spectrometry (LC/HRMS). Our results confirmed that all three genes are necessary for coprogen biosynthesis. Phenotypically, the mutants displayed growth differences under iron-deficient conditions, which correlated with their ability to either synthesize or fail to synthesize coprogen B and dimerumic acid, intermediates in the coprogen pathway with siderophore activity. Conclusions The results obtained in this work provide important insights into the molecular basis of coprogen biosynthesis in P. roqueforti, enhancing the understanding of how siderophores enable this fungus to thrive in iron-deficient environments. |
| format | Article |
| id | doaj-art-da2ddeca78fc44d2af622005fed3b237 |
| institution | DOAJ |
| issn | 0717-6287 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Biological Research |
| spelling | doaj-art-da2ddeca78fc44d2af622005fed3b2372025-08-20T03:04:10ZengBMCBiological Research0717-62872025-07-0158111410.1186/s40659-025-00633-2Molecular basis for the biosynthesis of the siderophore coprogen in the cheese-ripening fungus Penicillium roquefortiKathia González0Mariana Montanares1Matías Gallardo2Carlos Gil-Durán3Abel M. Forero4Jaime Rodríguez5Carlos Jiménez6Inmaculada Vaca7Renato Chávez8Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile (USACH)Departamento de Química, Facultad de Ciencias, Universidad de ChileDepartamento de Química, Facultad de Ciencias, Universidad de ChileDepartamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile (USACH)CICA-Centro Interdisciplinar de Química e Bioloxía, Departamento de Química, Facultade de Ciencias, Universidade da CoruñaCICA-Centro Interdisciplinar de Química e Bioloxía, Departamento de Química, Facultade de Ciencias, Universidade da CoruñaCICA-Centro Interdisciplinar de Química e Bioloxía, Departamento de Química, Facultade de Ciencias, Universidade da CoruñaDepartamento de Química, Facultad de Ciencias, Universidad de ChileDepartamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile (USACH)Abstract Background Iron is an essential nutrient for microorganisms, including fungi, which have evolved strategies to acquire it. The most common strategy is the secretion of siderophores, low-molecular-weight compounds with a high affinity for ferric ions, which are involved in cellular iron uptake. Penicillium roqueforti, the fungus responsible for the ripening of blue-veined cheeses, produces coprogen, a hydroxamate-type siderophore. However, to date, the molecular basis for its biosynthesis remains elusive. Results In this study, we identified and characterized a biosynthetic gene cluster (BGC) responsible for coprogen biosynthesis in P. roqueforti, named the cop BGC. This BGC contains seven genes, three of which (copA, copB and copE) encode enzymes directly involved in coprogen biosynthesis from precursors molecules. Using CRISPR-Cas9, we targeted these three genes and analyzed the resulting mutants by Liquid Chromatography/High-Resolution Mass Spectrometry (LC/HRMS). Our results confirmed that all three genes are necessary for coprogen biosynthesis. Phenotypically, the mutants displayed growth differences under iron-deficient conditions, which correlated with their ability to either synthesize or fail to synthesize coprogen B and dimerumic acid, intermediates in the coprogen pathway with siderophore activity. Conclusions The results obtained in this work provide important insights into the molecular basis of coprogen biosynthesis in P. roqueforti, enhancing the understanding of how siderophores enable this fungus to thrive in iron-deficient environments.https://doi.org/10.1186/s40659-025-00633-2Penicillium roquefortiSiderophoreCoprogenBiosynthetic gene clusterCRISPR-Cas9Mass spectrometry |
| spellingShingle | Kathia González Mariana Montanares Matías Gallardo Carlos Gil-Durán Abel M. Forero Jaime Rodríguez Carlos Jiménez Inmaculada Vaca Renato Chávez Molecular basis for the biosynthesis of the siderophore coprogen in the cheese-ripening fungus Penicillium roqueforti Biological Research Penicillium roqueforti Siderophore Coprogen Biosynthetic gene cluster CRISPR-Cas9 Mass spectrometry |
| title | Molecular basis for the biosynthesis of the siderophore coprogen in the cheese-ripening fungus Penicillium roqueforti |
| title_full | Molecular basis for the biosynthesis of the siderophore coprogen in the cheese-ripening fungus Penicillium roqueforti |
| title_fullStr | Molecular basis for the biosynthesis of the siderophore coprogen in the cheese-ripening fungus Penicillium roqueforti |
| title_full_unstemmed | Molecular basis for the biosynthesis of the siderophore coprogen in the cheese-ripening fungus Penicillium roqueforti |
| title_short | Molecular basis for the biosynthesis of the siderophore coprogen in the cheese-ripening fungus Penicillium roqueforti |
| title_sort | molecular basis for the biosynthesis of the siderophore coprogen in the cheese ripening fungus penicillium roqueforti |
| topic | Penicillium roqueforti Siderophore Coprogen Biosynthetic gene cluster CRISPR-Cas9 Mass spectrometry |
| url | https://doi.org/10.1186/s40659-025-00633-2 |
| work_keys_str_mv | AT kathiagonzalez molecularbasisforthebiosynthesisofthesiderophorecoprogeninthecheeseripeningfunguspenicilliumroqueforti AT marianamontanares molecularbasisforthebiosynthesisofthesiderophorecoprogeninthecheeseripeningfunguspenicilliumroqueforti AT matiasgallardo molecularbasisforthebiosynthesisofthesiderophorecoprogeninthecheeseripeningfunguspenicilliumroqueforti AT carlosgilduran molecularbasisforthebiosynthesisofthesiderophorecoprogeninthecheeseripeningfunguspenicilliumroqueforti AT abelmforero molecularbasisforthebiosynthesisofthesiderophorecoprogeninthecheeseripeningfunguspenicilliumroqueforti AT jaimerodriguez molecularbasisforthebiosynthesisofthesiderophorecoprogeninthecheeseripeningfunguspenicilliumroqueforti AT carlosjimenez molecularbasisforthebiosynthesisofthesiderophorecoprogeninthecheeseripeningfunguspenicilliumroqueforti AT inmaculadavaca molecularbasisforthebiosynthesisofthesiderophorecoprogeninthecheeseripeningfunguspenicilliumroqueforti AT renatochavez molecularbasisforthebiosynthesisofthesiderophorecoprogeninthecheeseripeningfunguspenicilliumroqueforti |