title: Comparative physiological effects of incorporated amino acid analogs in Escherichia coli.
abstract: The relative toxicities of several incorporated analogs of phenylalanine, methionine, arginine, and proline were assessed by a variety of criteria in a derivative of Escherichia coli 15 requiring the antagonized amino acids. Toxicity of the analog-substituted cell protein was most consistently indicated by its insolubility at graded temperatures, its increased breakdown, the relative suppression of further cell growth, and lethality. The relative toxicity of poorly utilized analogs could be judged clearly only by the first two criteria. Toxicity generally increased as follows: selenomethionine < 2,5-dihydrophenylalanine and m-fluorophenylalanine < o-fluorophenylalanine and norleucine < ethionine < p-fluorophenylalanine < azetidine-2-carboxylate < canavanine. The overall perturbation of cell protein structure indicated by the toxicity of the methionine and phenylalanine analogs correlated with their alteration of charge and bulk and was greatly modified by minor positional modifications of fluorine. Among the more specific functional impairments, the activity and heat stability of beta-galactosidase were lowered in parallel by substitutions of phenylalanine and methionine analogs, but not in the usual order of toxicity. Flagella were transiently motile with p-fluorophenylalanine, moderately motile with m-fluorophenylalanine, and fully motile with all methionine analogs. Usually the analog incorporations were no more than bacteriostatic in E. coli strains, canavanine killing only the E. coli 15 substrain extensively in minimal media. Selenomethionine supported indefinite growth of procaryotes such as Bacillus subtilis and certain E. coli strains, but only upon supplementation, at least initially, with many nonessential metabolites.
mesh_terms: D000596:Amino Acids / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000378:metabolism; D004269:DNA, Bacterial / Q000096:biosynthesis; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D005696:Galactosidases / Q000378:metabolism; D012329:RNA, Bacterial / Q000096:biosynthesis; D013997:Time Factors
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D012329:RNA, Bacterial; D005696:Galactosidases