Modulation of Multiple Gene Clusters’ Expression by the PAS-LuxR Transcriptional Regulator PteF
PAS-LuxR transcriptional regulators are conserved proteins governing polyene antifungal biosynthesis. PteF is the regulator of filipin biosynthesis from <i>Streptomyces avermitilis</i>. Its mutation drastically abates filipin, but also oligomycin production, a macrolide ATP-synthase inhi...
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MDPI AG
2022-07-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/8/994 |
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| author | Cláudia M. Vicente Tamara D. Payero Antonio Rodríguez-García Eva G. Barreales Antonio de Pedro Fernando Santos-Beneit Jesús F. Aparicio |
| author_facet | Cláudia M. Vicente Tamara D. Payero Antonio Rodríguez-García Eva G. Barreales Antonio de Pedro Fernando Santos-Beneit Jesús F. Aparicio |
| author_sort | Cláudia M. Vicente |
| collection | DOAJ |
| description | PAS-LuxR transcriptional regulators are conserved proteins governing polyene antifungal biosynthesis. PteF is the regulator of filipin biosynthesis from <i>Streptomyces avermitilis</i>. Its mutation drastically abates filipin, but also oligomycin production, a macrolide ATP-synthase inhibitor, and delays sporulation; thus, it has been considered a transcriptional activator. Transcriptomic analyses were performed in <i>S. avermitilis</i> Δ<i>pteF</i> and its parental strain. Both strains were grown in a YEME medium without sucrose, and the samples were taken at exponential and stationary growth phases. A total of 257 genes showed an altered expression in the mutant, most of them at the exponential growth phase. Surprisingly, despite PteF being considered an activator, most of the genes affected showed overexpression, thereby suggesting a negative modulation. The affected genes were related to various metabolic processes, including genetic information processing; DNA, energy, carbohydrate, and lipid metabolism; morphological differentiation; and transcriptional regulation, among others, but were particularly related to secondary metabolite biosynthesis. Notably, 10 secondary metabolite gene clusters out of the 38 encoded by the genome showed altered expression profiles in the mutant, suggesting a regulatory role for PteF that is wider than expected. The transcriptomic results were validated by quantitative reverse-transcription polymerase chain reaction. These findings provide important clues to understanding the intertwined regulatory machinery that modulates antibiotic biosynthesis in <i>Streptomyces</i>. |
| first_indexed | 2024-03-09T04:46:50Z |
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| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T04:46:50Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-573086844cdd4df2bcd46469bf4789502023-12-03T13:14:07ZengMDPI AGAntibiotics2079-63822022-07-0111899410.3390/antibiotics11080994Modulation of Multiple Gene Clusters’ Expression by the PAS-LuxR Transcriptional Regulator PteFCláudia M. Vicente0Tamara D. Payero1Antonio Rodríguez-García2Eva G. Barreales3Antonio de Pedro4Fernando Santos-Beneit5Jesús F. Aparicio6Department of Molecular Biology, Area of Microbiology, Faculty of Biology, Universidad de León, 24071 León, SpainDepartment of Molecular Biology, Area of Microbiology, Faculty of Biology, Universidad de León, 24071 León, SpainDepartment of Molecular Biology, Area of Microbiology, Faculty of Biology, Universidad de León, 24071 León, SpainDepartment of Molecular Biology, Area of Microbiology, Faculty of Biology, Universidad de León, 24071 León, SpainDepartment of Molecular Biology, Area of Microbiology, Faculty of Biology, Universidad de León, 24071 León, SpainInstitute of Biotechnology INBIOTEC, Parque Científico de León, Avda. Real, No 1, 24006 León, SpainDepartment of Molecular Biology, Area of Microbiology, Faculty of Biology, Universidad de León, 24071 León, SpainPAS-LuxR transcriptional regulators are conserved proteins governing polyene antifungal biosynthesis. PteF is the regulator of filipin biosynthesis from <i>Streptomyces avermitilis</i>. Its mutation drastically abates filipin, but also oligomycin production, a macrolide ATP-synthase inhibitor, and delays sporulation; thus, it has been considered a transcriptional activator. Transcriptomic analyses were performed in <i>S. avermitilis</i> Δ<i>pteF</i> and its parental strain. Both strains were grown in a YEME medium without sucrose, and the samples were taken at exponential and stationary growth phases. A total of 257 genes showed an altered expression in the mutant, most of them at the exponential growth phase. Surprisingly, despite PteF being considered an activator, most of the genes affected showed overexpression, thereby suggesting a negative modulation. The affected genes were related to various metabolic processes, including genetic information processing; DNA, energy, carbohydrate, and lipid metabolism; morphological differentiation; and transcriptional regulation, among others, but were particularly related to secondary metabolite biosynthesis. Notably, 10 secondary metabolite gene clusters out of the 38 encoded by the genome showed altered expression profiles in the mutant, suggesting a regulatory role for PteF that is wider than expected. The transcriptomic results were validated by quantitative reverse-transcription polymerase chain reaction. These findings provide important clues to understanding the intertwined regulatory machinery that modulates antibiotic biosynthesis in <i>Streptomyces</i>.https://www.mdpi.com/2079-6382/11/8/994antifungal agentgene regulationLuxRPAS domainpolyene macrolide<i>Streptomyces</i> |
| spellingShingle | Cláudia M. Vicente Tamara D. Payero Antonio Rodríguez-García Eva G. Barreales Antonio de Pedro Fernando Santos-Beneit Jesús F. Aparicio Modulation of Multiple Gene Clusters’ Expression by the PAS-LuxR Transcriptional Regulator PteF Antibiotics antifungal agent gene regulation LuxR PAS domain polyene macrolide <i>Streptomyces</i> |
| title | Modulation of Multiple Gene Clusters’ Expression by the PAS-LuxR Transcriptional Regulator PteF |
| title_full | Modulation of Multiple Gene Clusters’ Expression by the PAS-LuxR Transcriptional Regulator PteF |
| title_fullStr | Modulation of Multiple Gene Clusters’ Expression by the PAS-LuxR Transcriptional Regulator PteF |
| title_full_unstemmed | Modulation of Multiple Gene Clusters’ Expression by the PAS-LuxR Transcriptional Regulator PteF |
| title_short | Modulation of Multiple Gene Clusters’ Expression by the PAS-LuxR Transcriptional Regulator PteF |
| title_sort | modulation of multiple gene clusters expression by the pas luxr transcriptional regulator ptef |
| topic | antifungal agent gene regulation LuxR PAS domain polyene macrolide <i>Streptomyces</i> |
| url | https://www.mdpi.com/2079-6382/11/8/994 |
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