Corynecin Ⅳ

Chloramphenicol-3-acetate esterase activity was detected in cell-free extracts of strains of Streptomyces venezuela, Streptomyces sp. and Streptosporangium viridogriseum var. kofuense which produced chloramphenicol and also Corynebacterium hydrocarboclastus which produced chloramphenicol analogs (corynecins). None of the cell-free extracts of chloramphenicol- or corynecin-producing strains possessed chloramphenicol acetyltransferase activity under conditions which avoided the influenced of the esterase activity. Among 20 strains examined that did not produce chloramphenicol, chloramphenicol acetyltransferase was detected in cell-free extracts of one strain of Streptomyces coelicolor Müller and one strain of S. fradiae ISP5063.

Bacteriophage types of over 3,000 strains of Corynebacterium diphtheriae isolated in Canada have been determined. The typing scheme used involved the use of nine phages. Results indicated that phage types correlate with biotypes to a large degree. Corynecin types were also determined for a limited number of cultures, and results indicated that the indicator strains presently available are unsuitable for the typing of C. diphtheriae strains isolated in North America. The distribution of phage types is similar throughout Canada, and the types present correspond to types reported from other countries. Phage typing could be of value in the study of circumscribed outbreaks and in epidemiological surveillance of types over long periods.

Addition of p-aminophenylalanine (4), an advanced biosynthetic precursor of the antibiotic chloramphenicol (5), to a Streptomyces venezuelae pabAB mutant (VS629) restored chloramphenicol production and led to formation of the non-chlorinated analogue corynecin II (6) and four acetanilide derivatives: p-(acetylamino)phenylalanine (7), p-(acetylamino)benzyl alcohol (13), p-(acetylamino)benzoic acid (14), and p-(acetylamino)phenol (acetaminophen, 16). Metabolite structures were deduced from NMR and MS-MS data and established by chromatographic and spectroscopic comparisons with authentic samples. Reference compound 13 was synthesized by reducing the acid chloride of 14. Shunt pathways are proposed to account for the formation of the metabolites from p-aminophenylalanine.