基于Cas9的基因编辑的应用,用于非核糖体合成酶的工程
Takuya Hashimoto1, Hikaru Suenaga2, Kazuo Shin-Ya2
1Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566, Japan.
Chembiochem : a European journal of chemical biology
|December 31, 2024
概括
工程非核糖体合成酶 (NRPSs) 可以增强生物活性化合物生产. 将进化见解与CRISPR-Cas9基因编辑相结合,加速了新型NRPS组装线的开发,用于高产量的天然产品衍生品.
科学领域:
- 生物化学 生物化学
- 合成生物学 合成生物学
- 自然产品化学 自然产品化学
背景情况:
- 非核糖体合成酶 (NRPSs) 对于生产各种生物活性天然产品至关重要.
- 工程NRPS为新型衍生品提供了一条途径,但保持生产产量是具有挑战性的.
- 了解进化关系可以确定NRPS工程的最佳地点.
研究的目的:
- 探索工程NRPS的策略,以改善生物活性天然产品衍生物的生产.
- 利用比较基因组学和先进的基因编辑来优化NRPS装配线.
- 加速发现和可扩展生产有价值的自然产品.
主要方法:
- 对进化相关的NRPS进行比较分析,以确定允许的聚变地点.
- 工程NRPS利用已识别的重组站点.
- 基于CRISPR相关蛋白9 (Cas9) 的基因编辑的应用,用于修改大型生物合成基因集群 (BGCs).
- 大规模的信息学分析以指导工程策略.
主要成果:
- 在已识别的进化重组地点设计NRPS显示出显著的潜力,而不会影响产量.
- 克里斯普尔-Cas9技术可以精确编辑大型BGC (>100kb).
- 信息学和基因编辑的整合加速了NRPS工程的探索.
结论:
- 工程NRPS是转变自然产品衍生生产的可行策略.
- 将进化见解与CRISPR-Cas9基因编辑相结合,为NRPS优化提供了一个强大的工具包.
- 这种综合方法有望加速,可扩展的生产高产量的生物活性天然产品衍生物.
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