Biogenesis of an Antitumor Antibiotic Protein, Neocarzonostatin

ABSTRACT

A study of the biogenesis of the antitumor protein antibiotic neocarzinostatin (NCS) was undertaken. The production of NCS, as well as the growth of Streptomyces carzinostaticus in a production medium, was sensitive to puromycin, chloramphenicol, and actinomycin D. However, when a 12-hr culture in production medium was transferred to a nongrowth medium consisting of a phosphate buffer with Mg²⁺ and Ca²⁺, rapid NCS synthesis and liberation occurred. NCS production in this medium was no longer sensitive to actinomycin D, but was sensitive to puromycin and chloramphenicol. The conversion of a precursor NCS to an active form was shown to occur in this medium. Subcellular analysis suggested that NCS synthesis occurred by a mechanism similar to that of protein synthesis by membrane polysomes.