beta-lactam antibiotic production by Streptomyces clavuligerus mutants impaired in regulation of aspartokinase.
This work describes isolation and characterization of Streptomyces clavuligerus mutants resistant to the lysine analogue S-(2-aminoethyl)-L-cysteine (AEC). The mutation to AEC resistance was shown to affect the feedback regulation of aspartokinase; 70% of the mutants isolated had aspartokinase activity insensitive to concerted feedback inhibition by lysine plus threonine. Among these mutants, 70% (about 50% of the total AEC-resistant strains isolated) showed significant overproduction of beta-lactam antibiotics.
D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001222:Aspartate Kinase / Q000378:metabolism*; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D008239:Lysine / Q000494:pharmacology; D009154:Mutation; D010770:Phosphotransferases / Q000378:metabolism*; D013302:Streptomyces / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013912:Threonine / Q000494:pharmacology; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; C000204:S-2-aminoethyl cysteine; D013912:Threonine; D010770:Phosphotransferases; D001222:Aspartate Kinase; D008239:Lysine; D003545:Cysteine