Metabolites of a blocked chloramphenicol producer.
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.
Lewis
Elizabeth A
EA
Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, B3H 4J3 Canada.
Adamek
Tamara L
TL
Vining
Leo C
LC
White
Robert L
RL
D010129:4-Aminobenzoic Acid / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D002701:Chloramphenicol / Q000096:biosynthesis*; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013302:Streptomyces / Q000187:drug effects* / Q000201:enzymology*
D000900:Anti-Bacterial Agents; C009722:4-aminophenylalanine; D010649:Phenylalanine; D002701:Chloramphenicol; D010129:4-Aminobenzoic Acid