在里斯托米辛生物合成中的后糖变化的表征
Zhanzhao Cui1, Xiaozheng Wang1, Lixin Yin2,3
1State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
ACS chemical biology
|June 16, 2025
概括
这项研究揭示了ristomycin (ristocetin) 的组装后修改,这是一种糖类抗生素 (GPA). 了解这些步骤可以设计具有增强抗微生物活性的新型GPA.
科学领域:
- 微生物学 微生物学
- 生物化学 生物化学
- 合成生物学 合成生物学
背景情况:
- 里斯托米辛 (ristocetin) 是一种III型糖抗生素 (GPA),对抗格兰阳性病原体具有强大的活性.
- 里斯托米辛生物合成中的组装后定制步骤尚未完全理解,这阻碍了新型类型的开发.
研究的目的:
- 为了划出 postaglycone 调整步骤,以适应 ristomycin 成熟.
- 提出一个全面的ristomycin生物合成模型,包括糖化和甲基化.
- 为了识别具有改善抗微生物活性的ristomycin glycoforms.
主要方法:
- *Amycolatopsis* sp. 的生成和表征 在TNS106突变.
- 关键酶 (RgtfB,RgtfC,MtfA) 的体外生化分析.
- 将新发现与现有文献整合起来,构建一个生物合成模型.
主要成果:
- 证实了糖系转移酶 (RgtfB,RgtfC) 和甲基转移酶 (MtfA) 的功能和时间.
- 提出了一种对瑞斯托米辛糖化和C端甲基化的序列模型.
- 鉴定了具有增强抗微生物功效的里斯托米辛糖形式.
- 证明了特定的甘氨基基修饰 (例如,里斯托山胺去除,拉姆诺斯添加) 影响活性,特别是在对抗抗万科米辛耐药的Enterococcus.
结论:
- 该研究提供了一个详细的模型,用于ristomycin组装后的修改.
- 工程菌株为新型GPAs的组合生物合成提供了一个平台.
- 鉴定了具有改善活性的甘油形式,促进了GPA的发展.
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