非核糖体脂的工程生物合成与修改的脂肪酸侧链
Amanda Powell1, Mathew Borg, Bagher Amir-Heidari
1School of Chemistry, The University of Manchester, Oxford Road, Manchester, United Kingdom.
Journal of the American Chemical Society
|November 21, 2007
概括
取决于的抗生素 (CDA) 的活性与它们的脂肪酸链有关. 研究人员修改了CDA生物合成,以创建具有改变脂肪酸组的新脂,保持抗生素特性.
科学领域:
- 生物化学 生物化学
- 微生物学 微生物学
- 合成生物学 合成生物学
背景情况:
- 依赖性抗生素 (CDAs),如达普托米辛,是非核糖体脂.
- 它们的生物活性受到N端脂肪酸的显著影响.
- 生物合成途径和CDA脂肪酸链长度的酶控制尚未完全理解.
研究的目的:
- 研究KAS-II酶 (编码为fabF3) 和HxcO在确定CDA脂肪酸链长度方面的作用.
- 探索使用修饰脂肪酸部分生成新型CDA的可能性.
- 评估CDAs与改变的N端脂肪酸链的抗生素活性.
主要方法:
- 基因删除研究 (hxcO) 观察CDA产品的变化.
- 分析脂产品以确定脂肪酸链长度.
- 突变合成方法涉及CdaPS1.1的局部定向突变发生.
- 包括合成的N--L-氨酸N-乙烯基胺 (NAC) 类型的类型.
主要成果:
- 删除hxcO导致产生含有六醇的CDA (hCDA),证实了HxcO作为氧化酶的作用.
- 有证据表明,CDA脂质链生物合成发生在单个ACP上,然后转移到CdaPS1.
- 含赫萨诺伊尔的CDA保留了显著的抗生素活性.
- 突变合成使得使用类和六类侧链的CDAs可以产生.
结论:
- 在CDA中,HxcO对于产生特定的短脂肪酸链至关重要.
- CDA生物合成途径涉及单个ACP和直接转移到CdaPS1.
- 通过突变合成修改N端脂肪酸组是一种可行的策略,可以产生具有保留抗生素活性的新型CDA.
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