Bacillus subtilis Utilizes Decarboxylated S-Adenosylmethionine for the Biosynthesis of Tandem Aminopropylated Microcin C, a Potent Inhibitor of Bacterial Aspartyl-tRNA Synthetase DOI
Alexey Kulikovsky,

Eldar Yagmurov,

Anastasiia Grigoreva

и другие.

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

The biosynthetic pathways of natural products involve unusual biochemical reactions catalyzed by unique enzymes. Aminopropylation, although apparently simple, is an extremely rare modification outside polyamine biosynthesis. canonical pathway used in the biosynthesis peptide-adenylate antibiotic microcin C E. coli (Eco-McC) entails alkylation S-adenosyl-methionine-derived 3-amino-3-carboxypropyl group adenylate moiety and subsequent decarboxylation to yield bioactive aminopropylated compound. Here, we report structure a new member family antibiotics, Bsu-McC, produced Bacillus subtilis MG27, which employs alternative aminopropylation pathway. Like Eco-McC, Bsu-McC consists peptide that facilitates prodrug import into susceptible bacteria warhead, nonhydrolyzable modified isoasparaginyl-adenylate, which, when released cytoplasm, binds aspartyl-tRNA synthetase (AspRS) inhibiting translation. In contrast whose warhead carries single aminopropyl attached phosphate decorated with tandem two groups. Our silico docking AspRS-tRNA complex suggests groups form extended interactions enzyme tRNA, stabilizing enzyme–inhibitor complex. We show results 32-fold increase biological activity peptidyl-adenylate. also B. adopted for homologous 3-aminopropyltransferases utilize decarboxylated S-adenosylmethionine as substrate. Additionally, alters social behavior producer strain, resulting sharp decrease their ability biofilms.

Язык: Английский

Anti-MRSA and cytotoxic activity of a new diamide compound isolated from Aspergillus sp. H30 DOI

Long-Fen Li,

Yingying Hu, Xinzhu Wang

и другие.

Natural Product Research, Год журнала: 2025, Номер unknown, С. 1 - 7

Опубликована: Март 17, 2025

A new aromatic diamide compound, aspergillusin (1), together with three known compounds, globosterol (2), ergosterol (3), and cladosporide (4), was isolated from the crude extract of endophytic fungi Aspergillus sp. H30. The structures were elucidated using NMR MS data, finally, biosynthetic pathway compound 1 hypothesised. Compounds 1–4 tested for their antibacterial activities on six pathogenic bacteria also evaluated against human non-small cell lung cancer H1299. Among them, exhibited weak activity MRSA a strong effect bronchial epithelial line, BEAS-2B, an IC50 value 12.32 ± 0.37 μM.

Язык: Английский

Процитировано

0
Bacillus subtilis Utilizes Decarboxylated S-Adenosylmethionine for the Biosynthesis of Tandem Aminopropylated Microcin C, a Potent Inhibitor of Bacterial Aspartyl-tRNA Synthetase DOI
Alexey Kulikovsky,

Eldar Yagmurov,

Anastasiia Grigoreva

и другие.

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

The biosynthetic pathways of natural products involve unusual biochemical reactions catalyzed by unique enzymes. Aminopropylation, although apparently simple, is an extremely rare modification outside polyamine biosynthesis. canonical pathway used in the biosynthesis peptide-adenylate antibiotic microcin C E. coli (Eco-McC) entails alkylation S-adenosyl-methionine-derived 3-amino-3-carboxypropyl group adenylate moiety and subsequent decarboxylation to yield bioactive aminopropylated compound. Here, we report structure a new member family antibiotics, Bsu-McC, produced Bacillus subtilis MG27, which employs alternative aminopropylation pathway. Like Eco-McC, Bsu-McC consists peptide that facilitates prodrug import into susceptible bacteria warhead, nonhydrolyzable modified isoasparaginyl-adenylate, which, when released cytoplasm, binds aspartyl-tRNA synthetase (AspRS) inhibiting translation. In contrast whose warhead carries single aminopropyl attached phosphate decorated with tandem two groups. Our silico docking AspRS-tRNA complex suggests groups form extended interactions enzyme tRNA, stabilizing enzyme–inhibitor complex. We show results 32-fold increase biological activity peptidyl-adenylate. also B. adopted for homologous 3-aminopropyltransferases utilize decarboxylated S-adenosylmethionine as substrate. Additionally, alters social behavior producer strain, resulting sharp decrease their ability biofilms.

Язык: Английский

Процитировано

0