MUTANTS OF STREPTOMYCES-CATTLEYA DEFECTIVE IN THE SYNTHESIS OF A FACTOR REQUIRED FOR THIENAMYCIN PRODUCTION

Thienamycin non-producing mutants of Streptomydes cattleya were identi fied that displayed a cross-feeding relationship. A diffusible product from one of these mutants (RK-11) resulted in restoration of thienamy cin production when fed to cultures of another mutant (RK-4). In vivo radiolabeling experiments were conducted to test whether the RK-11 mut ant produced a late biosynthetic intermediate which contained a carbap enem ring and a cysteaminyl and/or a hydroxyethyl side chain. Both [S- 35]cystine and [methyl-H-3]methionine were used to label the RK-11 pro duct which was then fed to RK-4 cultures. None of the thienamycin subs equently produced by RK-4 converter cells was labeled, implying the la ck of either side chain of the thienamycin molecule in the RK-11 produ ct. Further stability studies suggested that the RK-11 product does no t contain a carbapenem ring. Additional feeding experiments with RK-4 cells also ruled out the possibility that the RK-11 product is a co-fa ctor necessary for thienamycin production. It is concluded that the RK -11 product may regulate expression of the thienamycin gene cluster.