在Bacillus subtilis中新型turnagainolides及其生物合成基因集群的解
Peng Li1,2, Shuang Han3, Min Wang4
1Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Health Science Center, Ningbo University, Ningbo, Zhejiang, China.
Applied and environmental microbiology
|April 25, 2025
概括
研究人员从Bacillus subtilis LP中发现了六种turnagainolides,扩大了这些周期性depsipeptides的知识. 该研究确定了它们的生物合成基因集群和途径,为自然产品药物发现提供了洞察力.
科学领域:
- 自然产品化学 自然产品化学
- 微生物学 微生物学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 甲基化物是具有多种生物活性的循环脱类,以前从各种微生物中鉴定出来.
- 生物合成基因集群和turnagainolides的途径以前是未知的.
- 微生物天然产品对于药物发现至关重要,因为它们的结构多样性和治疗潜力.
研究的目的:
- 为了识别和描述来自Bacillus subtilis LP. 的新型turnagainolide同源.
- 为了阐明生物合成基因集群和turnagainolides的途径.
- 研究turnagainolides在药物开发中的潜力,包括它们的生物膜抑制和细胞毒性活动.
主要方法:
- 使用LC-MS,NMR光谱学和莫舍衍生法分离和结构阐明甲化物.
- 基因组测序,遗传学分析和反SMASH预测,以确定生物合成基因集群 (tur-BGC).
- 基因淘汰实验证实了tur-BGC在turnagainolide生物合成中的作用.
主要成果:
- 从Bacillus subtilis LP.中确定了四种新的turnagainolide类原体 (D-G) 和两个已知的化合物 (A-B).
- 通过基因淘汰确定和验证了turnagainolides的完整生物合成基因集群 (tur-BGC).
- 对tur-BGC的同源蛋白质仅在细菌物种中发现,这表明了特定的进化血统.
结论:
- 这项研究扩大了Bacillus物种产生的循环的已知化学多样性.
- 已确定的生物合成途径为未来的代谢工程和turnagainolides的生产优化提供了基础.
- 甲基化物表现出生物膜抑制和细胞毒性活动,突出显示了它们在药物开发方面的潜力.
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