Dissolution of the Disparate: Co-ordinate Regulation in Antibiotic Biosynthesis
Discovering new antibiotics is vital to combat the growing threat of antimicrobial resistance. Most currently used antibiotics originate from the natural products of actinomycete bacteria, particularly <i>Streptomyces</i> species, that were discovered over 60 years ago. However, genome s...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-06-01
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| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/8/2/83 |
| _version_ | 1818947457230307328 |
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| author | Thomas C. McLean Barrie Wilkinson Matthew I. Hutchings Rebecca Devine |
| author_facet | Thomas C. McLean Barrie Wilkinson Matthew I. Hutchings Rebecca Devine |
| author_sort | Thomas C. McLean |
| collection | DOAJ |
| description | Discovering new antibiotics is vital to combat the growing threat of antimicrobial resistance. Most currently used antibiotics originate from the natural products of actinomycete bacteria, particularly <i>Streptomyces</i> species, that were discovered over 60 years ago. However, genome sequencing has revealed that most antibiotic-producing microorganisms encode many more natural products than previously thought. Biosynthesis of these natural products is tightly regulated by global and cluster situated regulators (CSRs), most of which respond to unknown environmental stimuli, and this likely explains why many biosynthetic gene clusters (BGCs) are not expressed under laboratory conditions. One approach towards novel natural product discovery is to awaken these cryptic BGCs by re-wiring the regulatory control mechanism(s). Most CSRs bind intergenic regions of DNA in their own BGC to control compound biosynthesis, but some CSRs can control the biosynthesis of multiple natural products by binding to several different BGCs. These cross-cluster regulators present an opportunity for natural product discovery, as the expression of multiple BGCs can be affected through the manipulation of a single regulator. This review describes examples of these different mechanisms, including specific examples of cross-cluster regulation, and assesses the impact that this knowledge may have on the discovery of novel natural products. |
| first_indexed | 2024-12-20T08:31:12Z |
| format | Article |
| id | doaj.art-ae91c6d407dd4043a58f797e0ae28408 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-12-20T08:31:12Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-ae91c6d407dd4043a58f797e0ae284082022-12-21T19:46:43ZengMDPI AGAntibiotics2079-63822019-06-01828310.3390/antibiotics8020083antibiotics8020083Dissolution of the Disparate: Co-ordinate Regulation in Antibiotic BiosynthesisThomas C. McLean0Barrie Wilkinson1Matthew I. Hutchings2Rebecca Devine3School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UKDepartment of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UKSchool of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UKSchool of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UKDiscovering new antibiotics is vital to combat the growing threat of antimicrobial resistance. Most currently used antibiotics originate from the natural products of actinomycete bacteria, particularly <i>Streptomyces</i> species, that were discovered over 60 years ago. However, genome sequencing has revealed that most antibiotic-producing microorganisms encode many more natural products than previously thought. Biosynthesis of these natural products is tightly regulated by global and cluster situated regulators (CSRs), most of which respond to unknown environmental stimuli, and this likely explains why many biosynthetic gene clusters (BGCs) are not expressed under laboratory conditions. One approach towards novel natural product discovery is to awaken these cryptic BGCs by re-wiring the regulatory control mechanism(s). Most CSRs bind intergenic regions of DNA in their own BGC to control compound biosynthesis, but some CSRs can control the biosynthesis of multiple natural products by binding to several different BGCs. These cross-cluster regulators present an opportunity for natural product discovery, as the expression of multiple BGCs can be affected through the manipulation of a single regulator. This review describes examples of these different mechanisms, including specific examples of cross-cluster regulation, and assesses the impact that this knowledge may have on the discovery of novel natural products.https://www.mdpi.com/2079-6382/8/2/83Secondary metabolismregulationbiosynthesisantibiotics |
| spellingShingle | Thomas C. McLean Barrie Wilkinson Matthew I. Hutchings Rebecca Devine Dissolution of the Disparate: Co-ordinate Regulation in Antibiotic Biosynthesis Antibiotics Secondary metabolism regulation biosynthesis antibiotics |
| title | Dissolution of the Disparate: Co-ordinate Regulation in Antibiotic Biosynthesis |
| title_full | Dissolution of the Disparate: Co-ordinate Regulation in Antibiotic Biosynthesis |
| title_fullStr | Dissolution of the Disparate: Co-ordinate Regulation in Antibiotic Biosynthesis |
| title_full_unstemmed | Dissolution of the Disparate: Co-ordinate Regulation in Antibiotic Biosynthesis |
| title_short | Dissolution of the Disparate: Co-ordinate Regulation in Antibiotic Biosynthesis |
| title_sort | dissolution of the disparate co ordinate regulation in antibiotic biosynthesis |
| topic | Secondary metabolism regulation biosynthesis antibiotics |
| url | https://www.mdpi.com/2079-6382/8/2/83 |
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