Effect of the proline analogue baikiain on proline metabolism in Salmonella typhimurium.
A proline analogue, 4,5-dehydro-l-pipecolic acid (baikiain) induces the formation in Salmonella typhimurium of the two enzymes catalyzing the degradation of proline, proline oxidase and Delta(1)-pyrroline-5-carboxylic acid (P5C) dehydrogenase. The level of induction by 20 mm baikiain is about 10% of the maximum level induced by proline. Since the analogue is a substrate of proline oxidase the first enzyme of the proline catabolic pathway, the oxidation derivative rather than baikiain itself might be the actual effector. Baikiain is also an inducer of proline oxidase in Escherichia coli K-12 and E. coli W. An additional effect of this analogue on proline degradation in S. typhimurium is inhibition of P5C dehydrogenase. At a concentration of 5 x 10(-4)m, baikiain inhibits completely the growth of strains constitutive for proline oxidase. This inhibition, which can be overcome by proline, occurs in the presence or absence of P5C dehydrogenase activity. Three spontaneously occurring mutants resistant to baikiain were isolated from constitutive strains. All are pleiotropic-negative for the proline-degrading enzymes. The sites of these mutations are linked to the put region. Although the mechanism of toxicity has not been determined, baikiain provides a simple and direct selection for obtaining mutants unable to degrade proline. In addition, it allows selection for strains with an inducible rather than constitutive phenotype.
D002384:Catalysis; D004352:Drug Resistance, Microbial; D004790:Enzyme Induction; D009154:Mutation; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010641:Phenotype; D010875:Pipecolic Acids / Q000494:pharmacology*; D011392:Proline / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development / Q000302:isolation & purification / Q000378:metabolism*; D013053:Spectrophotometry; D013237:Stereoisomerism; D014161:Transduction, Genetic
D010875:Pipecolic Acids; D011392:Proline; D010088:Oxidoreductases