2-Amino-3-methylthiobutyric Acid, an Isoleucine Antagonist<sup>1</sup>

McCord, Tommy J.; Howell, Drusilla Cook; Tharp, Don L.; Davis, Alvie L.

doi:10.1021/jm00327a004

Cited by 10 publications

(7 citation statements)

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“…The only description of its synthesis is by McCogo et al (11). Since the synthesis starts with symmetric compounds, the product must be a racemic mixture, but it has not been determined whether it is the DL-allo-mixture, the DL-threo-mixture or a mixture of all four forms.…”

Section: Thiaisoleucinementioning

confidence: 99%

“…The following procedure is essentially that of MCCORD et al (11) with the exception that 2-phenyl-4-ethylidene-5-oxazolone was synthesized by a slight modification of a more recent, better yielding procedure (13) than that of CARTER et al (5).…”

Section: Thiaisoleucinementioning

confidence: 99%

“…67778) in the presence of sodium methoxide as described by McCORD et al (11), but scaled up. Fortynine grams of the reaction product melting at 72-75~ were recovered by crystallization from ethanol at -20~ in 16 hours.…”

Section: Thiaisoleucinementioning

confidence: 99%

“…A small amount of this product was hydrolyzed to thiaisoleucine and the benzoic acid removed as described by MCCoRD et al (11). We could not get the thiaisoleucine hydrochloride to crystallize from the suspension in benzene described by McCORD et al Therefore, in a second preparation, instead of adding benzene to the oily acid residue containing the hydrochloride, this was diluted with distilled water, titrated to neutrality with sodium hydroxide and brought to dryness.…”

Section: Thiaisoleucinementioning

confidence: 99%

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Mutants in the biosynthesis of isoleucine in a non-mating, non-sporulating brewing strain of Saccharomyces carlsbergensis

Kielland‐Brandt

Petersen

Mikkelsen

1979

Carlsberg Res. Commun.

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Mutants resistant to 2-amino-3-(methylthio)butanoic acid (thiaisoleucine) were selected from a non-mating, nonsporulating brewing strain of Saccharomyces carlsbergensis after treatment with N-methyl-N'-nitro-Nnitrosoguanidine. One closer studied mutant, C77-T70 had a threonine deaminase activity which was less sensitive to L-isoleucine than that of the parent strain. The inhibition with varying concentrations of L-isoleucine showed that part of the activity was as sensitive as that of the parent strain, suggesting that the mutant is heterozygous for a dominant change in the structural gene for threonine deaminase. Of twelve mutants selected on 25 mM-thiaisoleucine all are believed to have undergone a change similar to that of C77-T70, since their threonine deaminase activity was partly resistant to 1 mM-L-isoleucine like that of C77-T70. Four such mutants were compared to the parent strain for the production of fusel alcohols during aerobic growth in minimal medium. The synthesis of 2-methyl-1 -butanol (D-amyl alcohol) was 2-5 times higher in the mutants than in the parent strain, while the syntheses in the mutants of 3-methyl-l-butanol (isoamyl alcohol) and 2-methyl-lpropanol (isobutanol) were similar or slightly reduced compared to the level found in the parent strain.

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Section: Thiaisoleucinementioning

confidence: 99%

Section: Thiaisoleucinementioning

confidence: 99%

Section: Thiaisoleucinementioning

confidence: 99%

Section: Thiaisoleucinementioning

confidence: 99%

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Mutants in the biosynthesis of isoleucine in a non-mating, non-sporulating brewing strain of Saccharomyces carlsbergensis

Kielland‐Brandt

Petersen

Mikkelsen

1979

Carlsberg Res. Commun.

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“…We considered that mutants lacking such feedback inhibition might be found among the class of mutants resistant to an analogue of isoleucine. Although cyclopentaneglycine, cyclohexene-1-glycine, and thiaisoleucine are known as isoleucine antagonists in some bacteria (3,4,9,16,19), a resistant mutant with an isoleucine-insensitive Lthreonine dehydratase has not been obtained.For these reasons, we attempted to search for other isoleucine antagonists in S. marcescens. Of several isoleucine analogues tested, isoleucine hydroxamate (Ile Hdx) was found to inhibit CH3-CH2 NH ,.…”

mentioning

confidence: 99%

Isoleucine Hydroxamate, an Isoleucine Antagonist

et al. 1971

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Isoleucine hydroxamate (Ile Hdx) was found to inhibit the growth of Serratia marcescens and to antagonize isoleucine. At a low concentration of Ile -Hdx, at which the growth of the wild strain was completely inhibited, the growth of an isoleucine auxotroph was not inhibited in the medium containing a limiting amount of D-threonine as the isoleucine source. At a higher concentration, this antagonist exhibited a considerable inhibitory effect on the growth of the auxotroph. IleoHdx showed the same inhibitory effect as isoleucine on L-threonine dehydratase activity at the concentrations 10 times those of isoleucine. Ile Hdx caused also derepression of isoleucine-valine biosynthetic enzymes and the derepression was overcome by isoleucine. These results indicate the Ile* Hdx causes growth inhibition by its effects on isoleucine metabolism.In the previous papers (13,14), it was reported that a-aminobutyric acid-resistant mutants of Serratia marcescens accumulated valine and accumulated isoleucine derived from D-threonine. Further investigation revealed some features of the regulatory mechanisms for isoleucine-valine biosynthesis in the wild strain and the basis of the genetic derepression of isoleucinevaline biosynthetic enzymes in the mutants (14a).It has been generally accepted that wild-type organisms do not accumulate isoleucine because of feedback control of L-threonine dehydratase. In view of the results on isoleucine accumulation in the presence of D-threonine (12, 13), it was anticipated that isoleucine would be overproduced from L-threonine by regulatory mutants of S. marcescens that lack feedback inhibition of Lthreonine dehydratase by isoleucine. We considered that mutants lacking such feedback inhibition might be found among the class of mutants resistant to an analogue of isoleucine. Although cyclopentaneglycine, cyclohexene-1-glycine, and thiaisoleucine are known as isoleucine antagonists in some bacteria (3,4,9,16,19), a resistant mutant with an isoleucine-insensitive Lthreonine dehydratase has not been obtained.For these reasons, we attempted to search for other isoleucine antagonists in S. marcescens. Of several isoleucine analogues tested, isoleucine hydroxamate (Ile Hdx) was found to inhibit CH3-CH2 NH ,. CH-CH-COOH CH3 Isolcucine CH3-CH2 NH2 , CH-CH-CONHOH CH3 Isoleucine hydroxomate (11e-Hdx)growth of S. marcescens. Ile*Hdx differs from isoleucine in having a CONHOH group instead of a COOH group. This paper deals with the bacteriostatic action of Ile Hdx. A separate paper will describe the properties of mutants resistant to this antagonist and the accumulation of isoleucine by feedback inhibition-negative mutants in L-threonine-containing media. MATERIALS AND METHODSBacteria. The bacterial strains used in this study were S. marcescens strain I (11) and the isoleucine auxotroph strain 420 derived from it.Growth experiments. Cultures were grown in test tubes (13 by 103 mm) containing 2 ml of Davis-Mingioli minimal medium (2) modified by omitting the citrate and increasing the glucose to 0.5%. Suppleme...

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Investigations on the Antiproliferative Effects of Amino Acid Antagonists Targeting for Aminoacyl‐tRNA Synthetases Part I ‐ The Antibacterial Effect

Laske

Schönenberger

Holler

1989

Archiv der Pharmazie

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Amino acid antagonists with proven or potentially inhibitory activities on aminoacyl-tRNA synthetases were tested for their antiproliferative effect against E. coli B. The compounds 4- and 6-fluoro-tryptophan, 5-methyltryptophan, selenocystine and beta-(2-thienyl)alanine gave strong growth inhibition in minimal medium, which disappeared after addition of structurally related natural amino acids or in an enriched broth. The inhibitory effect on amino-acyl-tRNA synthetases and the minimal inhibitory concentration for growth inhibition in minimal medium could not be correlated.

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2-Amino-3-methylthiobutyric Acid, an Isoleucine Antagonist¹

Cited by 10 publications

References 1 publication

Mutants in the biosynthesis of isoleucine in a non-mating, non-sporulating brewing strain of Saccharomyces carlsbergensis

Mutants in the biosynthesis of isoleucine in a non-mating, non-sporulating brewing strain of Saccharomyces carlsbergensis

Isoleucine Hydroxamate, an Isoleucine Antagonist

Investigations on the Antiproliferative Effects of Amino Acid Antagonists Targeting for Aminoacyl‐tRNA Synthetases Part I ‐ The Antibacterial Effect

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2-Amino-3-methylthiobutyric Acid, an Isoleucine Antagonist1

Cited by 10 publications

References 1 publication

Mutants in the biosynthesis of isoleucine in a non-mating, non-sporulating brewing strain of Saccharomyces carlsbergensis

Mutants in the biosynthesis of isoleucine in a non-mating, non-sporulating brewing strain of Saccharomyces carlsbergensis

Isoleucine Hydroxamate, an Isoleucine Antagonist

Investigations on the Antiproliferative Effects of Amino Acid Antagonists Targeting for Aminoacyl‐tRNA Synthetases Part I ‐ The Antibacterial Effect

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2-Amino-3-methylthiobutyric Acid, an Isoleucine Antagonist¹