Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, Taiwan.
Department of Wood Based Materials and Design, College of Agriculture, National Chiayi University, Chiayi 60004, Taiwan.
Mar Drugs. 2021 Apr 9;19(4):209. doi: 10.3390/md19040209.
Empedopeptins-eight amino acid cyclic lipopeptides-are calcium-dependent antibiotics that act against Gram-positive bacteria such as by inhibiting cell wall biosynthesis. However, to date, the biosynthetic mechanism of the empedopeptins has not been well identified. Through comparative genomics and metabolomics analysis, we identified empedopeptin and its new analogs from a marine bacterium, sp. YMA4. We then unveiled the empedopeptin biosynthetic gene cluster. The core nonribosomal peptide gene null-mutant strains (Δ, Δ, and Δ) could not produce empedopeptin, while dioxygenase gene null-mutant strains (Δ and Δ) produced several unique empedopeptin analogs. However, the antibiotic activity of Δ and Δ was significantly reduced compared with the wild-type, demonstrating that the hydroxylated amino acid residues of empedopeptin and its analogs are important to their antibiotic activity. Furthermore, we found seven bacterial strains that could produce empedopeptin-like cyclic lipopeptides using a genome mining approach. In summary, this study demonstrated that an integrated omics strategy can facilitate the discovery of potential bioactive metabolites from microbial sources without further isolation and purification.
Empedopeptins—八种氨基酸环状脂肽—是一类依赖于钙的抗生素，通过抑制细胞壁生物合成来对抗革兰氏阳性菌，如 。然而，迄今为止，empedopeptin 的生物合成机制尚未得到很好的鉴定。通过比较基因组学和代谢组学分析，我们从海洋细菌 中鉴定出 empedopeptin 及其新类似物。然后，我们揭示了 empedopeptin 的生物合成基因簇。核心非核糖体肽基因缺失突变株（Δ、Δ 和 Δ）不能产生 empedopeptin，而双加氧酶基因缺失突变株（Δ 和 Δ）则产生了几种独特的 empedopeptin 类似物。然而，与野生型相比，Δ 和 Δ 的抗生素活性显著降低，表明 empedopeptin 及其类似物中羟基化的氨基酸残基对其抗生素活性很重要。此外，我们还通过基因组挖掘方法发现了 7 株能够产生 empedopeptin 样环状脂肽的细菌。总之，这项研究表明，综合组学策略可以促进从微生物来源中发现潜在的生物活性代谢产物，而无需进一步的分离和纯化。
