THE EXPANDED HORIZON FOR MICROBIAL METABOLITES - A REVIEW

Modern screening methods have been used for a variety of new natural products. By taking advantage of the side effects of erythromycin, a derivative, EM523, and several related substances (motilides) have been synthesized. These compounds are agonists of the peptide hormone, motilin. By screening for microbial metabolites which may substitute for biologically active peptides, we discovered lactacystin. It has nerve growth-factor-like activity and induces differentiation in mouse neuroblastoma Neuro2A cells. An inhibitor of protein kinase, staurosporine, a microbial alkaloid found by chemical screening, has a variety of pharmacological activities, such as the relaxation of rabbit aortic strips and the inhibition of changes in platelet shape induced with phorbol myristate acetate. Triacsin, an inhibitor of acetyl-CoA synthetase, which was isolated from Streptomyces sp. SK-1894, potentiated platelet-activating factor production of A23187-treated rat polymorphonuclear leukocytes. Phthoxazolin, an inhibitor of cellulose biosynthesis isolated from Streptomyces sp. OM-5714, inhibited the growth of velvet leaf when treated after its emergence. These products provide examples of the possible utility of newly discovered microbial metabolites.