三种酶级联催化了在查特鲁素生物合成中将奥拉amycinone转化为resomycin的过程
Magdalena Niemczura1, Aleksi Nuutila1, Rongbin Wang1
1Department of Life Technologies, University of Turku, FIN-20014 Turku, Finland.
ACS chemical biology
|July 2, 2025
概括
研究人员确定了三种对图列素生物合成至关重要的酶,详细介绍了通过不同的脱水反应将奥拉美辛转化为Resomycin C的过程. 这一发现澄清了生产这种强大的抗增殖剂的最后步骤.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 合成生物学 合成生物学
背景情况:
- 查特鲁辛是一种强有力的抗增殖剂,具有独特的五环双乳支架.
- 第二种类型的多基基酸甘生物合成涉及四环四环林中间体,其最终步骤是以前未知的Resomycin C.
研究的目的:
- 阐明 chartreusin 生物合成中的最后一个酶性步骤,特别是 auramycinone 转化为 C. resomycin 的过程.
- 为了识别和描述负责这两种机理上不同的脱水反应的酶.
主要方法:
- 生物化学测试以表征酶活性.
- 生物合成途径的体外复制.
- 在 *Streptomyces coelicolor* M1152Δ*matAB* 中进行基因操纵和异质表达.
主要成果:
- 发现了三种酶:ChaX (一种氨酸减少酶),ChaU (一种类似循环酶的酶) 和ChaJ (一种同源的类似循环酶的酶).
- 通过一个carbanion中间体,ChaX和ChaU催化了9,10-dehydroauramycinone的形成.
- 通过一个碳酸介质,ChaJ催化了随后的7,8脱水,从而产生Resomycin C.
- 成功组装了生物合成途径,以在工程*Streptomyces coelicolor*中产生树脂素C.
结论:
- 这项研究揭示了从黄氨酸中进行Resomycin C生物合成的完整酶途径.
- 扩大了SnoaL蛋白家族已知的催化功能,超出了循环和氧化.
- 提供了一个潜在的工程 chartreusin 生产或相关化合物的基础.
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