Transport of L-4-azaleucine in Escherichia coli

Harrison, Lester I.; Christensen, Halvor N.; Handlogten, Mary E.; Oxender, Dale L.; Quay, Steven C.

doi:10.1128/jb.122.3.957-965.1975

Cited by 13 publications

(5 citation statements)

References 24 publications

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“…From the synthetic sequence outlined in Scheme 2 it is evident that the absolute configuration of the product amino acid (8) derives directly from the chiral aspartic acid employed in the synthesis of the starting complex 1. As a consequence of the additional stereogenic centre in the octahedral tris(didentate) coordination mode of this complex, initial separation of the ∆-S-1 and Λ-S-1 isomers was required in order to have isomerically pure reactants.…”

Section: Discussionmentioning

confidence: 99%

“…Alkylation of the primary N 3 -amine of Λ-S-6 with formaldehyde and NaBH 3 CN in aqueous acetic acid/acetate buffer 65 afforded the dimethylated derivative (7) in high yield. Reduction of this complex with zinc dust in acid and chromatographic separation of the liberated ligands led to isolation of the enantiopure free amino acid (8) dihydrochloride. This has been obtained before, also in a metal-aided synthesis, but less enantiopure.…”

Section: Synthesesmentioning

confidence: 99%

“…The bacterial growth inhibitor (S)-2-amino-3-(N,N-dimethylamino)propanoic acid [S-A 2 pr(Me 2 )] produced by Streptomyces neocaliberis acts as an antimetabolite for leucine of which it is an isostere ("4-Scheme 1 azaleucine"). 8 Other microbial metabolites which also include the S-A 2 pr unit, comprise the fungal aspergillomarasmin plant toxins 9 and several peptide antibiotics, 10-18 e.g. all members of the bleomycin 10, 11 and malonomicin 12 families.…”

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confidence: 99%

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Novel metal complex synthons for chiral 4-azaleucine, 2,3-diaminopropanoic acid and its elaboration

Barfod¹,

Bendahl²,

Hammershøi³

et al. 1999

J. Chem. Soc., Dalton Trans.

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Efficient syntheses of chiral Co() complexes with 2,3-diaminopropanoic acid (A 2 pr) have been developed. In these complexes, the amino acid zwitterion [A 2 pr(H ϩ )O Ϫ ] is bound didentate through the carboxylate and N 2 -amine groups while the N 3 -ammonio group [pK a = 7.19(2)] is unprotected. Syntheses of Λ(ϩ) 578 -and ∆(Ϫ) 578 -[(en) 2 Co-(S-A 2 pr(H ϩ )O)]Cl 3 ؒH 2 O were effected stereoretentively from the similarly didentate aspartato complexes Λand ∆-[(en) 2 Co(S-Asp(OH)O)]Cl 2 in reaction sequences transforming the unbound β-carboxyl group into an amine by Curtius rearrangement. The absolute configuration of the Λ(ϩ) 578 -[(en) 2 Co(S-Asp(OH)O)](ClO 4 ) 2 complex was determined by X-ray crystallographic analysis and defined the absolute stereochemistry of diastereoisomers and derived products. Methylation of the N 3 -amine group of Λ(ϩ) 578 -[(en) 2 Co(S-A 2 pr(H ϩ )O)]Cl 3 ؒH 2 O gave the (S)-4azaleucine complex Λ(ϩ) 578 -[(en) 2 Co(S-A 2 pr(Me 2 H ϩ )O)](C 4 F 9 SO 3 ) 3 from which enantiopure (ϩ)-(S)-2-amino-3-(dimethylamino)propanoic acid dihydrochloride hemihydrate [=(ϩ)-(S)-A 2 pr(Me 2 )ؒ2HClؒ0.5H 2 O] was obtained upon reductive removal of the protecting Co(III) centre. Racemic 4-azaleucine was easily produced by an alternative, but also metal-dependent method and the intermediate rac-(p)-[(tren)Co(A 2 pr(Me 2 H ϩ )O)]Zn 2 Cl 7 ؒ3H 2 O obtained in a simple solid-phase synthesis by selective reduction of achiral (p)-[(tren)Co(2-amino-3-(dimethylamino)acrylyl chloride)] 3ϩ ion adsorbed on AG 50W-X2 cation exchange resin. The epimerization rate of the Λ-[(en) 2 Co(S-A 2 prO)] 2ϩ complex ion was first-order in [HO Ϫ ] [k E = 3.8 × 10 Ϫ2 dm 3 mol Ϫ1 s Ϫ1 , I = 1.00 M (NaClO 4 ), 25 ЊC] with the diastereoisomer ratio K C (=[Λ-R]/[Λ-S]) = 0.77(2) at equilibrium in 10 mM NaOH. However, no epimerization was observed after at least 3 hours in 6 M HCl at 45 ЊC.

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Section: Discussionmentioning

confidence: 99%

Section: Synthesesmentioning

confidence: 99%

mentioning

confidence: 99%

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Novel metal complex synthons for chiral 4-azaleucine, 2,3-diaminopropanoic acid and its elaboration

Barfod¹,

Bendahl²,

Hammershøi³

et al. 1999

J. Chem. Soc., Dalton Trans.

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“…Exodus experiments. The exodus of radiolabeled amino acids from cells was performed as described previously (12). Cells were grown, harvested, and washed thrice as described above.…”

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confidence: 99%

Role of transport systems in amino acid metabolism: leucine toxicity and the branched-chain amino acid transport systems

Quay¹,

Dick²,

Oxender³

1977

J Bacteriol

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The livR locus, which leads to a trans-recessive derepression of branchedchain amino acid transport and periplasmic branched-chain amino acid-binding proteins, is responsible for greatly increased sensitivity toward growth inhibition by leucine, valine, and serine and, as shown previously, for increased sensitivity toward toxicity by branched-chain amino acid analogues, such as 4azaleucine or 5',5',5'-triflvoroleucine. These phenotypes are similar to those of relA mutants; however, the livR mutants retain the stringent response of ribonucleic acid synthesis. However, an increase in the rate of transport or in the steady-state intracellular level of amino acids in the livR strain cannot completely account for this sensitivity. The ability of the LIV-I transport system to carry out exchange of pool amino acids for extracellular leucine is a major factor in leucine sensitivity. The previous finding that inhibition of threonine deaminase by leucine contributes to growth inhibition is confirmed by simulating the in vivo conditions using a toluene-treated cell preparation with added amino acids at levels corresponding to the internal pool. The relationship between transport systems and corresponding biosynthetic pathways is discussed and the general principle of a coordination in the regulation of transport and biosynthetic pathways is forwarded. The finding that the LIV-I transport system functions well for amino acid exchange in contrast to the LIV-Il system provides another feature that distinguishes these systems in addition to previously described differences in regulation and energetics.

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“…On the other hand, B. pumilus 150a contained AzlC and AzlD genes that codify for branched-chain amino acid transport proteins possibly involved in conferring resistance to 4-azaleucine—previously detected in other Bacillus genomes, but not in any other B. pumilus ( 11 , 12 ). This leucine analogue is a potent growth inhibitor in several bacteria due to its incorporation into proteins in place of leucine ( 13 , 14 ). 4-Azaleucine is produced by Streptomyces ( 15 ), one of the most abundant Actinobacteria in Cuatrociénegas ( 16 ).…”

Section: Genome Announcementmentioning

confidence: 99%

Complete Genome Sequences of Two Bacillus pumilus Strains from Cuatrociénegas, Coahuila, Mexico

et al. 2018

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We assembled the complete genome sequences of Bacillus pumilus strains 145 and 150a from Cuatrociénegas, Mexico. We detected genes codifying for proteins potentially involved in antagonism (bacteriocins) and defense mechanisms (abortive infection bacteriophage proteins and 4-azaleucine resistance). Both strains harbored prophage sequences. Our results provide insights into understanding the establishment of microbial interactions.

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Transport of L-4-azaleucine in Escherichia coli

Cited by 13 publications

References 24 publications

Novel metal complex synthons for chiral 4-azaleucine, 2,3-diaminopropanoic acid and its elaboration

Novel metal complex synthons for chiral 4-azaleucine, 2,3-diaminopropanoic acid and its elaboration

Role of transport systems in amino acid metabolism: leucine toxicity and the branched-chain amino acid transport systems

Complete Genome Sequences of Two Bacillus pumilus Strains from Cuatrociénegas, Coahuila, Mexico

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