Fungal BGCs for Production of Secondary Metabolites: Main Types, Central Roles in Strain Improvement, and Regulation According to the Piano Principle
Filamentous fungi are one of the most important producers of secondary metabolites. Some of them can have a toxic effect on the human body, leading to diseases. On the other hand, they are widely used as pharmaceutically significant drugs, such as antibiotics, statins, and immunosuppressants. A sing...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/13/11184 |
| _version_ | 1797591516357591040 |
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| author | Alexander A. Zhgun |
| author_facet | Alexander A. Zhgun |
| author_sort | Alexander A. Zhgun |
| collection | DOAJ |
| description | Filamentous fungi are one of the most important producers of secondary metabolites. Some of them can have a toxic effect on the human body, leading to diseases. On the other hand, they are widely used as pharmaceutically significant drugs, such as antibiotics, statins, and immunosuppressants. A single fungus species in response to various signals can produce 100 or more secondary metabolites. Such signaling is possible due to the coordinated regulation of several dozen biosynthetic gene clusters (BGCs), which are mosaically localized in different regions of fungal chromosomes. Their regulation includes several levels, from pathway-specific regulators, whose genes are localized inside BGCs, to global regulators of the cell (taking into account changes in pH, carbon consumption, etc.) and global regulators of secondary metabolism (affecting epigenetic changes driven by velvet family proteins, LaeA, etc.). In addition, various low-molecular-weight substances can have a mediating effect on such regulatory processes. This review is devoted to a critical analysis of the available data on the “turning on” and “off” of the biosynthesis of secondary metabolites in response to signals in filamentous fungi. To describe the ongoing processes, the model of “piano regulation” is proposed, whereby pressing a certain key (signal) leads to the extraction of a certain sound from the “musical instrument of the fungus cell”, which is expressed in the production of a specific secondary metabolite. |
| first_indexed | 2024-03-11T01:38:34Z |
| format | Article |
| id | doaj.art-e39b6a1c6fd045ab8a464deed92e81ab |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:38:34Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e39b6a1c6fd045ab8a464deed92e81ab2023-11-18T16:49:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124131118410.3390/ijms241311184Fungal BGCs for Production of Secondary Metabolites: Main Types, Central Roles in Strain Improvement, and Regulation According to the Piano PrincipleAlexander A. Zhgun0Group of Fungal Genetic Engineering, Federal Research Center “Fundamentals of Biotechnology”, Russian Academy of Sciences, Leninsky Prosp. 33-2, 119071 Moscow, RussiaFilamentous fungi are one of the most important producers of secondary metabolites. Some of them can have a toxic effect on the human body, leading to diseases. On the other hand, they are widely used as pharmaceutically significant drugs, such as antibiotics, statins, and immunosuppressants. A single fungus species in response to various signals can produce 100 or more secondary metabolites. Such signaling is possible due to the coordinated regulation of several dozen biosynthetic gene clusters (BGCs), which are mosaically localized in different regions of fungal chromosomes. Their regulation includes several levels, from pathway-specific regulators, whose genes are localized inside BGCs, to global regulators of the cell (taking into account changes in pH, carbon consumption, etc.) and global regulators of secondary metabolism (affecting epigenetic changes driven by velvet family proteins, LaeA, etc.). In addition, various low-molecular-weight substances can have a mediating effect on such regulatory processes. This review is devoted to a critical analysis of the available data on the “turning on” and “off” of the biosynthesis of secondary metabolites in response to signals in filamentous fungi. To describe the ongoing processes, the model of “piano regulation” is proposed, whereby pressing a certain key (signal) leads to the extraction of a certain sound from the “musical instrument of the fungus cell”, which is expressed in the production of a specific secondary metabolite.https://www.mdpi.com/1422-0067/24/13/11184secondary metabolitesbiosynthetic gene clusters (BGCs)filamentous fungiglobal regulationLaeA |
| spellingShingle | Alexander A. Zhgun Fungal BGCs for Production of Secondary Metabolites: Main Types, Central Roles in Strain Improvement, and Regulation According to the Piano Principle International Journal of Molecular Sciences secondary metabolites biosynthetic gene clusters (BGCs) filamentous fungi global regulation LaeA |
| title | Fungal BGCs for Production of Secondary Metabolites: Main Types, Central Roles in Strain Improvement, and Regulation According to the Piano Principle |
| title_full | Fungal BGCs for Production of Secondary Metabolites: Main Types, Central Roles in Strain Improvement, and Regulation According to the Piano Principle |
| title_fullStr | Fungal BGCs for Production of Secondary Metabolites: Main Types, Central Roles in Strain Improvement, and Regulation According to the Piano Principle |
| title_full_unstemmed | Fungal BGCs for Production of Secondary Metabolites: Main Types, Central Roles in Strain Improvement, and Regulation According to the Piano Principle |
| title_short | Fungal BGCs for Production of Secondary Metabolites: Main Types, Central Roles in Strain Improvement, and Regulation According to the Piano Principle |
| title_sort | fungal bgcs for production of secondary metabolites main types central roles in strain improvement and regulation according to the piano principle |
| topic | secondary metabolites biosynthetic gene clusters (BGCs) filamentous fungi global regulation LaeA |
| url | https://www.mdpi.com/1422-0067/24/13/11184 |
| work_keys_str_mv | AT alexanderazhgun fungalbgcsforproductionofsecondarymetabolitesmaintypescentralrolesinstrainimprovementandregulationaccordingtothepianoprinciple |