TY - JOUR
T1 - Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain Streptomyces albidoflavus J1074
AU - Dolya, Borys
AU - Hryhorieva, Olena
AU - Sorochynska , Khrystyna
AU - Lopatniuk , Maria
AU - Ostash , Iryna
AU - Tseduliak , Vasylyna-Marta
AU - Sterndorff, Eva Baggesgaard
AU - Jørgensen, Tue Sparholt
AU - Gren, Tetiana
AU - Dacyuk, Yuriy
AU - Weber, Tilmann
AU - Luzhetskyy , Andriy
AU - Fedorenko, Victor
AU - Ostash, Bohdan
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Streptomyces albidoflavus J1074
KW - Rifampicin resistance
KW - rpoB
KW - Specialized metabolites
U2 - 10.3390/microorganisms11051176
DO - 10.3390/microorganisms11051176
M3 - Journal article
C2 - 37317150
SN - 2076-2607
VL - 11
JO - Microorganisms
JF - Microorganisms
M1 - 1176
ER -