八糖核的生物合成起源及其在阿普拉胺生物合成过程中的组装机制
Po-Hsun Fan1, Shusuke Sato2, Yu-Cheng Yeh1
1Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, United States.
Journal of the American Chemical Society
|September 21, 2023
概括
研究人员发现了一种新型酶AprG, 这一发现揭示了使用N-乙氨糖形成的新 [6+2] 生物合成途径.
科学领域:
- 生物化学
- 分子生物学
- 抗生素生物合成
背景情况:
- 阿普拉是一种兽用氨基糖类抗生素,具有独特的八度成分.
- 对于阿普拉米辛的八度核的生物合成途径在很大程度上是未知的.
- 之前的研究表明,N-乙氨糖是八度糖组合的前体.
研究的目的:
- 阐明在阿普拉米辛生物合成中形成八核的机制.
- 在这个过程中描述AprG酶的功能.
主要方法:
- 对AprG蛋白序列的生物信息分析.
- AprG的表达和净化
- 使用N-乙氨糖和6'-oxo-lividamine进行体外酶测定.
主要成果:
- AprG催化了N-乙氨糖 (GlcNAc或GalNAc) 和6'-氧-利维达胺之间的转反应.
- 这种反应产生的7'-N-乙甲基胺具有特定的立体化学反应,与阿普拉米辛一致.
- 这表明了一种新的 [6+2] 氧化物生物合成途径与一个反转的双碳供体.
结论:
- AprG是一种新型的转酶,与其他酶没有已知的序列相似性.
- 鉴定的途径代表了生物八形成的新机制.
- 这一发现显著提高了对阿普拉米辛生物合成的理解.
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