1. Mutants of Streptomyces cattleya defective in the synthesis of a factor required for thienamycin production
- Author
-
Tim Buchan, Claudia Roach, Carol Preisig, Carolyn L. Ruby, Christopher D. Reeves, and Dean P. Taylor
- Subjects
Stereochemistry ,Mutant ,Sulfur Radioisotopes ,Tritium ,medicine.disease_cause ,Streptomyces ,chemistry.chemical_compound ,Methionine ,Biosynthesis ,Drug Discovery ,polycyclic compounds ,medicine ,Chromatography, High Pressure Liquid ,Antibacterial agent ,Pharmacology ,Streptomyces cattleya ,biology ,Streptomycetaceae ,Temperature ,Hydrogen-Ion Concentration ,biology.organism_classification ,Thienamycin ,chemistry ,Biochemistry ,Ethyl Methanesulfonate ,Mutation ,Cystine ,Thienamycins - Abstract
Thienamycin non-producing mutants of Streptomydes cattleya were identified that displayed a cross-feeding relationship. A diffusible product from one of these mutants (RK-11) resulted in restoration of thienamycin production when fed to cultures of another mutant (RK-4). In vivo radiolabeling experiments were conducted to test whether the RK-11 mutant produced a late biosynthetic intermediate which contained a carbapenem ring and a cysteaminyl and/or a hydroxyethyl side chain. Both [35S]cystine and [methyl-3H]methionine were used to label the RK-11 product which was then fed to RK-4 cultures. None of the thienamycin subsequently produced by RK-4 converter cells was labeled, implying the lack of either side chain of the thienamycin molecule in the RK-11 product. Further stability studies suggested that the RK-11 product does not contain a carbapenem ring. Additional feeding experiments with RK-4 cells also ruled out the possibility that the RK-11 product is a co-factor necessary for thienamycin production. It is concluded that the RK-11 product may regulate expression of the thienamycin gene cluster.
- Published
- 1994