Novel natural products are urgently needed to address the worldwide incidence of bacterial resistance to antibiotics. Extreme environments are a major source of novel compounds with unusual chemical structures. Pedobacter lusitanus NL19 is a new bacterial species that was isolated from one such environment and which produces compounds with potent activity against relevant microorganisms in the clinical, food, veterinary and aquaculture areas. The production of antimicrobials by P. lusitanus NL19 was identified in tryptic soy agar (TSA), but not in its equivalent broth (TSB). It was observed that in TSB medium a high concentration of casein peptone (PC) repressed the production of antibacterial compounds. HPLC, MS and MS/MS spectra with de novo sequencing revealed that the bioactivity of P. lusitanus NL19 was due to the production of pedopeptins. Hence, biosynthesis of pedopeptins is inhibited by high concentrations of PC in the broth medium. Furthermore, a nonribosomal peptide synthetase (NRPS) gene cluster was identified in the genome of NL19 encoding the biosynthesis of the peptides. qPCR analysis confirmed that the transcription of these genes is repressed in cells cultivated in high concentrations of PC. It is shown that pedopeptins are nonribosomal peptides with a broad-spectrum activity, including against Gram-positive and Gram-negative bacteria and yeasts.

中文翻译：

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酪蛋白胨，一种非核糖体肽合成的拮抗剂：一个关于 Pedobacter lusitanus NL19 pedopeptins 的案例研究

迫切需要新型天然产品来解决全球范围内细菌对抗生素耐药的问题。极端环境是具有不寻常化学结构的新型化合物的主要来源。Pedobacter lusitanus NL19 是一种新的细菌物种，它是从这样的环境中分离出来的，它产生的化合物对临床、食品、兽医和水产养殖领域的相关微生物具有强效活性。P. lusitanus NL19 在胰蛋白酶大豆琼脂 (TSA) 中发现了抗微生物剂的产生，但在其等效肉汤 (TSB) 中没有发现。据观察，在 TSB 培养基中，高浓度的酪蛋白胨 (PC) 抑制了抗菌化合物的产生。具有 de novo 测序的 HPLC、MS 和 MS/MS 谱表明 P. lusitanus NL19 的生物活性是由于肽肽素的产生。因此，肉汤培养基中高浓度的 PC 抑制了足肽素的生物合成。此外，在编码肽生物合成的 NL19 基因组中发现了一个非核糖体肽合成酶 (NRPS) 基因簇。qPCR 分析证实，在高浓度 PC 培养的细胞中，这些基因的转录受到抑制。结果表明，pedopeptins 是具有广谱活性的非核糖体肽，包括抗革兰氏阳性和革兰氏阴性细菌和酵母菌。qPCR 分析证实，在高浓度 PC 培养的细胞中，这些基因的转录受到抑制。结果表明，pedopeptins 是具有广谱活性的非核糖体肽，包括抗革兰氏阳性和革兰氏阴性细菌和酵母菌。qPCR 分析证实，在高浓度 PC 培养的细胞中，这些基因的转录受到抑制。结果表明，pedopeptins 是具有广谱活性的非核糖体肽，包括抗革兰氏阳性和革兰氏阴性细菌和酵母菌。