Engineering of the Filamentous Fungus Penicillium chrysogenum as Cell Factory for Natural Products
Penicillium chrysogenum (renamed P. rubens) is the most studied member of a family of more than 350 Penicillium species that constitute the genus. Since the discovery of penicillin by Alexander Fleming, this filamentous fungus is used as a commercial β-lactam antibiotic producer. For several decades...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2018.02768/full |
| _version_ | 1811233599398084608 |
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| author | Fernando Guzmán-Chávez Fernando Guzmán-Chávez Reto D. Zwahlen Reto D. Zwahlen Roel A. L. Bovenberg Roel A. L. Bovenberg Arnold J. M. Driessen Arnold J. M. Driessen |
| author_facet | Fernando Guzmán-Chávez Fernando Guzmán-Chávez Reto D. Zwahlen Reto D. Zwahlen Roel A. L. Bovenberg Roel A. L. Bovenberg Arnold J. M. Driessen Arnold J. M. Driessen |
| author_sort | Fernando Guzmán-Chávez |
| collection | DOAJ |
| description | Penicillium chrysogenum (renamed P. rubens) is the most studied member of a family of more than 350 Penicillium species that constitute the genus. Since the discovery of penicillin by Alexander Fleming, this filamentous fungus is used as a commercial β-lactam antibiotic producer. For several decades, P. chrysogenum was subjected to a classical strain improvement (CSI) program to increase penicillin titers. This resulted in a massive increase in the penicillin production capacity, paralleled by the silencing of several other biosynthetic gene clusters (BGCs), causing a reduction in the production of a broad range of BGC encoded natural products (NPs). Several approaches have been used to restore the ability of the penicillin production strains to synthetize the NPs lost during the CSI. Here, we summarize various re-activation mechanisms of BGCs, and how interference with regulation can be used as a strategy to activate or silence BGCs in filamentous fungi. To further emphasize the versatility of P. chrysogenum as a fungal production platform for NPs with potential commercial value, protein engineering of biosynthetic enzymes is discussed as a tool to develop de novo BGC pathways for new NPs. |
| first_indexed | 2024-04-12T11:22:29Z |
| format | Article |
| id | doaj.art-c2736210bbd44a3aae52095392cc18fd |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-12T11:22:29Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-c2736210bbd44a3aae52095392cc18fd2022-12-22T03:35:19ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-11-01910.3389/fmicb.2018.02768409073Engineering of the Filamentous Fungus Penicillium chrysogenum as Cell Factory for Natural ProductsFernando Guzmán-Chávez0Fernando Guzmán-Chávez1Reto D. Zwahlen2Reto D. Zwahlen3Roel A. L. Bovenberg4Roel A. L. Bovenberg5Arnold J. M. Driessen6Arnold J. M. Driessen7Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, NetherlandsSynthetic Biology and Cell Engineering, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, NetherlandsMolecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, NetherlandsSynthetic Biology and Cell Engineering, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, NetherlandsSynthetic Biology and Cell Engineering, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, NetherlandsDSM Biotechnology Centre, Delft, NetherlandsMolecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, NetherlandsSynthetic Biology and Cell Engineering, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, NetherlandsPenicillium chrysogenum (renamed P. rubens) is the most studied member of a family of more than 350 Penicillium species that constitute the genus. Since the discovery of penicillin by Alexander Fleming, this filamentous fungus is used as a commercial β-lactam antibiotic producer. For several decades, P. chrysogenum was subjected to a classical strain improvement (CSI) program to increase penicillin titers. This resulted in a massive increase in the penicillin production capacity, paralleled by the silencing of several other biosynthetic gene clusters (BGCs), causing a reduction in the production of a broad range of BGC encoded natural products (NPs). Several approaches have been used to restore the ability of the penicillin production strains to synthetize the NPs lost during the CSI. Here, we summarize various re-activation mechanisms of BGCs, and how interference with regulation can be used as a strategy to activate or silence BGCs in filamentous fungi. To further emphasize the versatility of P. chrysogenum as a fungal production platform for NPs with potential commercial value, protein engineering of biosynthetic enzymes is discussed as a tool to develop de novo BGC pathways for new NPs.https://www.frontiersin.org/article/10.3389/fmicb.2018.02768/fullPenicillium chrysogenumnatural productsnonribosomal peptidespolyketidesgene activationbiosynthetic gene clusters |
| spellingShingle | Fernando Guzmán-Chávez Fernando Guzmán-Chávez Reto D. Zwahlen Reto D. Zwahlen Roel A. L. Bovenberg Roel A. L. Bovenberg Arnold J. M. Driessen Arnold J. M. Driessen Engineering of the Filamentous Fungus Penicillium chrysogenum as Cell Factory for Natural Products Frontiers in Microbiology Penicillium chrysogenum natural products nonribosomal peptides polyketides gene activation biosynthetic gene clusters |
| title | Engineering of the Filamentous Fungus Penicillium chrysogenum as Cell Factory for Natural Products |
| title_full | Engineering of the Filamentous Fungus Penicillium chrysogenum as Cell Factory for Natural Products |
| title_fullStr | Engineering of the Filamentous Fungus Penicillium chrysogenum as Cell Factory for Natural Products |
| title_full_unstemmed | Engineering of the Filamentous Fungus Penicillium chrysogenum as Cell Factory for Natural Products |
| title_short | Engineering of the Filamentous Fungus Penicillium chrysogenum as Cell Factory for Natural Products |
| title_sort | engineering of the filamentous fungus penicillium chrysogenum as cell factory for natural products |
| topic | Penicillium chrysogenum natural products nonribosomal peptides polyketides gene activation biosynthetic gene clusters |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2018.02768/full |
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