Reverse transsulfuration and its relationship to thienamycin biosynthesis in Streptomyces cattleya

Cystathionine gamma-lyase (EC 4.4.1.1) was purified from Streptomyces cattleya, an actinomycete which produces the unusual beta-lactam antibiotic thienamycin. The enzyme displays broad substrate specificity and is similar to gamma-lyases purified from other microorganisms. That the gamma-lyase functions in vivo to provide cysteine for antibiotic synthesis was shown by two types of experiments. First, cystathionine and methionine, as well as cysteine itself, are efficiently utilized by S. cattleya for thienamycin biosynthesis. Second, propargylglycine, a mechanism-based inactivator of cystathionine gamma-lyase in vitro, inhibits the synthesis of thienamycin in vivo. This inhibition can be substantially reversed by providing the cells with another source of cysteine, such as cystine.