Cargando…
Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain Streptomyces albidoflavus J1074
Streptomyces albidoflavus 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 specialize...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10220713/ https://www.ncbi.nlm.nih.gov/pubmed/37317150 http://dx.doi.org/10.3390/microorganisms11051176 |
_version_ | 1785049283473440768 |
---|---|
author | Dolya, Borys Hryhorieva, Olena Sorochynska, Khrystyna Lopatniuk, Maria Ostash, Iryna Tseduliak, Vasylyna-Marta Sterndorff, Eva Baggesgaard Jørgensen, Tue Sparholt Gren, Tetiana Dacyuk, Yuriy Weber, Tilmann Luzhetskyy, Andriy Fedorenko, Victor Ostash, Bohdan |
author_facet | Dolya, Borys Hryhorieva, Olena Sorochynska, Khrystyna Lopatniuk, Maria Ostash, Iryna Tseduliak, Vasylyna-Marta Sterndorff, Eva Baggesgaard Jørgensen, Tue Sparholt Gren, Tetiana Dacyuk, Yuriy Weber, Tilmann Luzhetskyy, Andriy Fedorenko, Victor Ostash, Bohdan |
author_sort | Dolya, Borys |
collection | PubMed |
description | Streptomyces albidoflavus 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 rpoB for the β-subunit of RNA polymerase are known to increase rifampicin resistance and augment the metabolic capabilities of streptomycetes. Yet, the effects of rpoB mutations on J1074 remained unstudied, and we decided to address this issue. A target collection of strains that we studied carried spontaneous rpoB 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 rpoB mutants showing various degrees of rifampicin resistance; one of them (S433W) was isolated for the first time in actinomycetes. The rpoB mutations had a major effect on antibiotic production by J1074, as evident from bioassays and LC-MS data. Our data support the idea that rpoB mutations are useful tools to enhance the ability of J1074 to produce specialized metabolites. |
format | Online Article Text |
id | pubmed-10220713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102207132023-05-28 Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain Streptomyces albidoflavus J1074 Dolya, Borys Hryhorieva, Olena Sorochynska, Khrystyna Lopatniuk, Maria Ostash, Iryna Tseduliak, Vasylyna-Marta Sterndorff, Eva Baggesgaard Jørgensen, Tue Sparholt Gren, Tetiana Dacyuk, Yuriy Weber, Tilmann Luzhetskyy, Andriy Fedorenko, Victor Ostash, Bohdan Microorganisms Article Streptomyces albidoflavus 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 rpoB for the β-subunit of RNA polymerase are known to increase rifampicin resistance and augment the metabolic capabilities of streptomycetes. Yet, the effects of rpoB mutations on J1074 remained unstudied, and we decided to address this issue. A target collection of strains that we studied carried spontaneous rpoB 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 rpoB mutants showing various degrees of rifampicin resistance; one of them (S433W) was isolated for the first time in actinomycetes. The rpoB mutations had a major effect on antibiotic production by J1074, as evident from bioassays and LC-MS data. Our data support the idea that rpoB mutations are useful tools to enhance the ability of J1074 to produce specialized metabolites. MDPI 2023-04-30 /pmc/articles/PMC10220713/ /pubmed/37317150 http://dx.doi.org/10.3390/microorganisms11051176 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Dolya, Borys Hryhorieva, Olena Sorochynska, Khrystyna Lopatniuk, Maria Ostash, Iryna Tseduliak, Vasylyna-Marta Sterndorff, Eva Baggesgaard Jørgensen, Tue Sparholt Gren, Tetiana Dacyuk, Yuriy Weber, Tilmann Luzhetskyy, Andriy Fedorenko, Victor Ostash, Bohdan Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain Streptomyces albidoflavus J1074 |
title | Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain Streptomyces albidoflavus J1074 |
title_full | Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain Streptomyces albidoflavus J1074 |
title_fullStr | Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain Streptomyces albidoflavus J1074 |
title_full_unstemmed | Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain Streptomyces albidoflavus J1074 |
title_short | Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain Streptomyces albidoflavus J1074 |
title_sort | properties of multidrug-resistant mutants derived from heterologous expression chassis strain streptomyces albidoflavus j1074 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10220713/ https://www.ncbi.nlm.nih.gov/pubmed/37317150 http://dx.doi.org/10.3390/microorganisms11051176 |
work_keys_str_mv | AT dolyaborys propertiesofmultidrugresistantmutantsderivedfromheterologousexpressionchassisstrainstreptomycesalbidoflavusj1074 AT hryhorievaolena propertiesofmultidrugresistantmutantsderivedfromheterologousexpressionchassisstrainstreptomycesalbidoflavusj1074 AT sorochynskakhrystyna propertiesofmultidrugresistantmutantsderivedfromheterologousexpressionchassisstrainstreptomycesalbidoflavusj1074 AT lopatniukmaria propertiesofmultidrugresistantmutantsderivedfromheterologousexpressionchassisstrainstreptomycesalbidoflavusj1074 AT ostashiryna propertiesofmultidrugresistantmutantsderivedfromheterologousexpressionchassisstrainstreptomycesalbidoflavusj1074 AT tseduliakvasylynamarta propertiesofmultidrugresistantmutantsderivedfromheterologousexpressionchassisstrainstreptomycesalbidoflavusj1074 AT sterndorffevabaggesgaard propertiesofmultidrugresistantmutantsderivedfromheterologousexpressionchassisstrainstreptomycesalbidoflavusj1074 AT jørgensentuesparholt propertiesofmultidrugresistantmutantsderivedfromheterologousexpressionchassisstrainstreptomycesalbidoflavusj1074 AT grentetiana propertiesofmultidrugresistantmutantsderivedfromheterologousexpressionchassisstrainstreptomycesalbidoflavusj1074 AT dacyukyuriy propertiesofmultidrugresistantmutantsderivedfromheterologousexpressionchassisstrainstreptomycesalbidoflavusj1074 AT webertilmann propertiesofmultidrugresistantmutantsderivedfromheterologousexpressionchassisstrainstreptomycesalbidoflavusj1074 AT luzhetskyyandriy propertiesofmultidrugresistantmutantsderivedfromheterologousexpressionchassisstrainstreptomycesalbidoflavusj1074 AT fedorenkovictor propertiesofmultidrugresistantmutantsderivedfromheterologousexpressionchassisstrainstreptomycesalbidoflavusj1074 AT ostashbohdan propertiesofmultidrugresistantmutantsderivedfromheterologousexpressionchassisstrainstreptomycesalbidoflavusj1074 |