Design and evaluation of novel analogs of 2-amino-4-boronobutanoic acid (ABBA) as inhibitors of human gamma-glutamyl transpeptidase

Nguyen, Luong; Schultz, Daniel; Terzyan, Simon; Rezaei, Mohammad; Song, Jun; Li, Chenglong; You, Youngjae; Hanigan, Marie H.

doi:10.1016/j.bmc.2022.116986

Cited by 4 publications

(3 citation statements)

References 60 publications

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“…LuxP, the sensor of the borate diester containing quorum sensing autoinducer-2 (Chen et al, 2002). Interestingly, even covalent bonds between boron atoms of organoboron compounds and amino acid side chains of proteins have been reported (Newman et al, 2021;Nguyen et al, 2022) and could potentially be involved in tartrolon is being exported at a higher rate than tartrolon A in the presence of the timABR cassette. This latter conclusion is in good agreement with the observation that the timABR promoter is stronger activated by tartrolon B as compared to tartrolon A.…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, TimR could make direct contacts with the borate ester part of the tartrolon B molecule through electrostatic interactions or could form hydrogen bonds with the borate oxygens as observed in Vibrio harveyi LuxP, the sensor of the borate diester containing quorum sensing autoinducer‐2 (Chen et al., 2002). Interestingly, even covalent bonds between boron atoms of organoboron compounds and amino acid side chains of proteins have been reported (Newman et al., 2021; Nguyen et al., 2022) and could potentially be involved in tartrolon B recognition by TimR.…”

Section: Discussionmentioning

confidence: 99%

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Tartrolon sensing and detoxification by the Listeria monocytogenes timABR resistance operon

Engelgeh,

Herrmann,

Jansen

et al. 2023

Molecular Microbiology

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Listeria monocytogenes is a foodborne bacterium that naturally occurs in the soil. Originating from there, it contaminates crops and infects farm animals and their consumption by humans may lead to listeriosis, a systemic life‐threatening infectious disease. The adaptation of L. monocytogenes to such contrastive habitats is reflected by the presence of virulence genes for host infection and other genes for survival under environmental conditions. Among the latter are ABC transporters for excretion of antibiotics produced by environmental competitors; however, most of these transporters have not been characterized. Here, we generated a collection of promoter‐lacZ fusions for genes encoding ABC‐type drug transporters of L. monocytogenes and screened this reporter strain collection for induction using a library of natural compounds produced by various environmental microorganisms. We found that the timABR locus (lmo1964‐lmo1962) was induced by the macrodiolide antibiotic tartrolon B, which is synthesized by the soil myxobacterium Sorangium cellulosum. Tartrolon B resistance of L. monocytogenes was dependent on timAB, encoding the ATPase and the permease component of a novel ABC transporter. Moreover, transplantation of timAB was sufficient to confer tartrolon B resistance to Bacillus subtilis. Expression of the timABR locus was found to be auto‐repressed by the TimR repressor, whose repressing activity was lost in the presence of tartrolon B. We also demonstrate that tartrolon sensitivity was suppressed by high external potassium concentrations, suggesting that tartrolon acts as potassium ionophore. Our results help to map the ecological interactions of an important human pathogen with its co‐residing species within their joint natural reservoir.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tartrolon sensing and detoxification by the Listeria monocytogenes timABR resistance operon

Engelgeh,

Herrmann,

Jansen

et al. 2023

Molecular Microbiology

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show abstract

“…Alternatively, TimR could make direct contacts with the borate ester part of the tartrolon B molecule through electrostatic interactions or could form hydrogen bonds with the borate oxygens as observed in Vibrio harveyi LuxP, the sensor of the borate diester containing quorum sensing autoinducer-2 (57). Interestingly, even covalent bonds between boron atoms of organoboron compounds and amino acid side chains of proteins have been reported (58,59) and could potentially be involved in tartrolon B recognition by TimR. Despite this remarkable specificity of TimR for tartrolon B, tartrolon detoxification by TimAB is not sensitive to the presence of the borate ester, as judged from the timAB transplantation experiment into B. subtilis.…”

Section: Discussionmentioning

confidence: 99%

Tartrolon sensing and detoxification by theListeria monocytogenes timABRresistance operon

Engelgeh

Herrmann

Jansen

et al. 2023

Preprint

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Listeria monocytogenes is a foodborne bacterium that naturally occurs in the soil. Originating from there, it contaminates crops and infects farm animals and their consumption by humans may lead to listeriosis, a systemic life-threatening infectious disease. The adaptation of L. monocytogenes to such contrastive habitats is reflected by the presence of virulence genes for host infection and other genes for survival under environmental conditions. Among the latter are ABC transporters for excretion of antibiotics produced by environmental competitors, however, most of these transporters have not been characterized. Here, we generated a collection of promoter-lacZ fusions of genes encoding ABC-type drug transporters of L. monocytogenes and screened this reporter strain collection for induction using a library of natural compounds produced by various environmental microorganisms. We found that the timABR locus (lmo1964-lmo1962) was induced by the macrodiolide antibiotic tartrolon B, which is synthesized by the soil myxobacterium Sorangium cellulosum. Tartrolon B resistance of L. monocytogenes was dependent on timAB, encoding the ATPase and the permease component of a novel ABC transporter. Moreover, transplantation of timAB was sufficient to confer tartrolon B resistance to Bacillus subtilis. Expression of the timABR locus was found to be auto-repressed by the TimR repressor, whose repressing activity was lost in the presence of tartrolon B. We also demonstrate that tartrolon sensitivity was suppressed by high external potassium concentrations, suggesting that tartrolon acts as potassium ionophore. Our results help to map the ecological interactions of an important human pathogen with its co-residing species within their joint natural reservoir.

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SAR of L-ABBA analogs for GGT1 inhibitory activity and L-ABBA's effect on plasma cysteine and GSH species

Bist,

Luong,

Mahabubur Rahman

et al. 2023

Bioorganic & Medicinal Chemistry Letters

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Design and evaluation of novel analogs of 2-amino-4-boronobutanoic acid (ABBA) as inhibitors of human gamma-glutamyl transpeptidase

Cited by 4 publications

References 60 publications

Tartrolon sensing and detoxification by the Listeria monocytogenes timABR resistance operon

Tartrolon sensing and detoxification by the Listeria monocytogenes timABR resistance operon

Tartrolon sensing and detoxification by theListeria monocytogenes timABRresistance operon

SAR of L-ABBA analogs for GGT1 inhibitory activity and L-ABBA's effect on plasma cysteine and GSH species

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