作为抗生素组装线中的凝结催化剂的转胺酶同类物
Pascal D Fortin1, Christopher T Walsh, Nathan A Magarvey
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|July 27, 2007
概括
一个新发现的酶,AdmF,作为一个转谷氨酸酶 (TGase) 在andrimid抗生素生物合成中形成第一个胺键. 这一发现为设计新型抗生素和发现新的生物合成途径开辟了道路.
科学领域:
- 生物化学和分子生物学
- 自然产品生物合成 自然产品生物合成
- 发现了抗生素的发现
背景情况:
- 抗生素耐药性需要具有独特作用机制的新型抗生素.
- 安德里米德是细菌脂肪酸生物合成的强有力的伪抑制剂.
- 安德里米德 (adm) 基因集群已被分离并表达在大肠杆菌中进行进一步研究.
研究的目的:
- 为了确定负责andrimid生物合成中的初始胺基键形成的酶.
- 描述这种新型酶在andrimid组装线中的功能.
- 探索转胺酶 (TGase) 同类物在天然产品生物合成中的潜力.
主要方法:
- 安德里米德 (adm) 基因集群的生物信息分析.
- 在大肠杆菌中adm集群的异质表达.
- 鉴定出的酶的生物化学特征,AdmF.
主要成果:
- 生物信息分析显示,adm集群中缺乏正规的胺合成酶.
- 确定AdmF,一种转氨酶 (TGase) 同类酶,是催化第一个胺基键形成的酶 (N--β-链).
- 在抗生素组装线上,AdmF作为独立的胺基合成酶起作用,将与蛋白质结合的基质连接起来.
结论:
- AdmF代表了一个新发现的生物合成酶,TGase同类物,用于抗生素组装.
- 这项研究报告了TGase类酶在抗生素生物合成中的第一次实例.
- 寻找TGase同源的基因组挖掘可以揭示新的天然产品生物合成途径和潜在的新抗生素.
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