Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain <i>Streptomyces albidoflavus</i> J1074
<i>Streptomyces albidoflavus</i> J1074 is a popular platform to discover novel natural products via the expression of heterologous biosynthetic gene clusters (BGCs). There is keen interest in improving the ability of this platform to overexpress BGCs and, consequently, enable the purific...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/11/5/1176 |
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| author | Borys Dolya Olena Hryhorieva Khrystyna Sorochynska Maria Lopatniuk Iryna Ostash Vasylyna-Marta Tseduliak Eva Baggesgaard Sterndorff Tue Sparholt Jørgensen Tetiana Gren Yuriy Dacyuk Tilmann Weber Andriy Luzhetskyy Victor Fedorenko Bohdan Ostash |
| author_facet | Borys Dolya Olena Hryhorieva Khrystyna Sorochynska Maria Lopatniuk Iryna Ostash Vasylyna-Marta Tseduliak Eva Baggesgaard Sterndorff Tue Sparholt Jørgensen Tetiana Gren Yuriy Dacyuk Tilmann Weber Andriy Luzhetskyy Victor Fedorenko Bohdan Ostash |
| author_sort | Borys Dolya |
| collection | DOAJ |
| description | <i>Streptomyces albidoflavus</i> J1074 is a popular platform to discover novel natural products via the expression of heterologous biosynthetic gene clusters (BGCs). There is keen interest in improving the ability of this platform to overexpress BGCs and, consequently, enable the purification of specialized metabolites. Mutations within gene <i>rpoB</i> for the β-subunit of RNA polymerase are known to increase rifampicin resistance and augment the metabolic capabilities of streptomycetes. Yet, the effects of <i>rpoB</i> mutations on J1074 remained unstudied, and we decided to address this issue. A target collection of strains that we studied carried spontaneous <i>rpoB</i> mutations introduced in the background of the other drug resistance mutations. The antibiotic resistance spectra, growth, and specialized metabolism of the resulting mutants were interrogated using a set of microbiological and analytical approaches. We isolated 14 different <i>rpoB</i> mutants showing various degrees of rifampicin resistance; one of them (S433W) was isolated for the first time in actinomycetes. The <i>rpoB</i> mutations had a major effect on antibiotic production by J1074, as evident from bioassays and LC-MS data. Our data support the idea that <i>rpoB</i> mutations are useful tools to enhance the ability of J1074 to produce specialized metabolites. |
| first_indexed | 2024-03-11T03:27:59Z |
| format | Article |
| id | doaj.art-074ec5aa5e7f49d4be3db5ee7c5b30f6 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-11T03:27:59Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-074ec5aa5e7f49d4be3db5ee7c5b30f62023-11-18T02:32:55ZengMDPI AGMicroorganisms2076-26072023-04-01115117610.3390/microorganisms11051176Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain <i>Streptomyces albidoflavus</i> J1074Borys Dolya0Olena Hryhorieva1Khrystyna Sorochynska2Maria Lopatniuk3Iryna Ostash4Vasylyna-Marta Tseduliak5Eva Baggesgaard Sterndorff6Tue Sparholt Jørgensen7Tetiana Gren8Yuriy Dacyuk9Tilmann Weber10Andriy Luzhetskyy11Victor Fedorenko12Bohdan Ostash13Department of Genetics and Biotechnology, Ivan Franko National University of Lviv, 79005 Lviv, UkraineDepartment of Genetics and Biotechnology, Ivan Franko National University of Lviv, 79005 Lviv, UkraineDepartment of Genetics and Biotechnology, Ivan Franko National University of Lviv, 79005 Lviv, UkraineDepartment of Pharmacy, Saarland University, 66123 Saarbrucken, GermanyDepartment of Genetics and Biotechnology, Ivan Franko National University of Lviv, 79005 Lviv, UkraineDepartment of Genetics and Biotechnology, Ivan Franko National University of Lviv, 79005 Lviv, UkraineThe Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet, 2800 Kongens Lyngby, DenmarkThe Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet, 2800 Kongens Lyngby, DenmarkThe Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet, 2800 Kongens Lyngby, DenmarkDepartment of Mineral Geology and Geophysics, Ivan Franko National University of Lviv, 79005 Lviv, UkraineThe Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet, 2800 Kongens Lyngby, DenmarkDepartment of Pharmacy, Saarland University, 66123 Saarbrucken, GermanyDepartment of Genetics and Biotechnology, Ivan Franko National University of Lviv, 79005 Lviv, UkraineDepartment of Genetics and Biotechnology, Ivan Franko National University of Lviv, 79005 Lviv, Ukraine<i>Streptomyces albidoflavus</i> J1074 is a popular platform to discover novel natural products via the expression of heterologous biosynthetic gene clusters (BGCs). There is keen interest in improving the ability of this platform to overexpress BGCs and, consequently, enable the purification of specialized metabolites. Mutations within gene <i>rpoB</i> for the β-subunit of RNA polymerase are known to increase rifampicin resistance and augment the metabolic capabilities of streptomycetes. Yet, the effects of <i>rpoB</i> mutations on J1074 remained unstudied, and we decided to address this issue. A target collection of strains that we studied carried spontaneous <i>rpoB</i> mutations introduced in the background of the other drug resistance mutations. The antibiotic resistance spectra, growth, and specialized metabolism of the resulting mutants were interrogated using a set of microbiological and analytical approaches. We isolated 14 different <i>rpoB</i> mutants showing various degrees of rifampicin resistance; one of them (S433W) was isolated for the first time in actinomycetes. The <i>rpoB</i> mutations had a major effect on antibiotic production by J1074, as evident from bioassays and LC-MS data. Our data support the idea that <i>rpoB</i> mutations are useful tools to enhance the ability of J1074 to produce specialized metabolites.https://www.mdpi.com/2076-2607/11/5/1176<i>Streptomyces albidoflavus</i> J1074rifampicin resistance<i>rpoB</i>specialized metabolites |
| spellingShingle | Borys Dolya Olena Hryhorieva Khrystyna Sorochynska Maria Lopatniuk Iryna Ostash Vasylyna-Marta Tseduliak Eva Baggesgaard Sterndorff Tue Sparholt Jørgensen Tetiana Gren Yuriy Dacyuk Tilmann Weber Andriy Luzhetskyy Victor Fedorenko Bohdan Ostash Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain <i>Streptomyces albidoflavus</i> J1074 Microorganisms <i>Streptomyces albidoflavus</i> J1074 rifampicin resistance <i>rpoB</i> specialized metabolites |
| title | Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain <i>Streptomyces albidoflavus</i> J1074 |
| title_full | Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain <i>Streptomyces albidoflavus</i> J1074 |
| title_fullStr | Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain <i>Streptomyces albidoflavus</i> J1074 |
| title_full_unstemmed | Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain <i>Streptomyces albidoflavus</i> J1074 |
| title_short | Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain <i>Streptomyces albidoflavus</i> J1074 |
| title_sort | properties of multidrug resistant mutants derived from heterologous expression chassis strain i streptomyces albidoflavus i j1074 |
| topic | <i>Streptomyces albidoflavus</i> J1074 rifampicin resistance <i>rpoB</i> specialized metabolites |
| url | https://www.mdpi.com/2076-2607/11/5/1176 |
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