Enhanced Antibiotic Production by Inducing Low Level of Resistance to Gentamicin

ABSTRACTAIMTo investigate the gentamicin-resistant mutants and find the relationship between resistance to gentamicin and enhanced antibiotic production.METHODSThe mutants with low level of resistance to gentamicin were selected and their antibiotic productivity was detected. Moreover, the stability of mutants was improved by a serial passage in the absence of gentamicin, and the expression of proteins ActII-ORF4 and RedD (and RedZ) in the mutants and parent were analysized and compared by Western Blotting.RESULTSMutants with enhanced antibiotic production were detected at a high frequency (3% to 20%) compared to traditional strain improving method. Moreover, Western blot analyses revealed that gentamicin-resistant (gen) mutations could activate/enhance actionorhodin (Act) and undecylprodigosin (Red) biosyntheses in Streptomyces lividans through directly or indirectly upregulating the expression of proteins ActII-ORF4 and RedD (and RedZ), the Act and Red biosynthesis pathway-specific positive regulators, respectively.CONCLUSIONA rational approach for improving the production of antibiotics in Streptomyces and other bacteria by inducing low level of resistance to gentamicin was developed.