工程酵母底盘的构建和优化,以实现8-基醇的高效生物合成
Yu Zhang1,2,3, Mengdi Yuan1, Xinxin Wu1
1BGI Research Shenzhen China.
mLife
|May 31, 2024
概括
现在,人工酵母产生的8-基基拉尼的含量超过了30倍. 微生物生物合成的这一进步利用了合成酵母和改进的geraniol 8-hydroxylase酶用于制药化合物生产.
科学领域:
- 合成生物学 合成生物学
- 代谢工程是代谢工程.
- 生物技术是生物技术.
背景情况:
- 微生物生产单类醇类化合物 (MIAs) 为有价值的药品提供了可持续的途径.
- 有效的MIA生物合成受到前体供应的限制,特别是日列和8-基日列.
- 葛兰醇8-基酶 (G8H) 对于8-基葛兰醇的生产至关重要.
研究的目的:
- 开发一种工程酵母菌株,用于增强8-基醇生产.
- 识别和优化geraniol 8-hydroxylase (G8H) 酶,以提高它们的活性.
- 通过优化代谢途径来增加8-基醇的产量.
主要方法:
- 在Sc2.0合成酵母中利用SCRaMbLE系统进行菌株演化和选.
- 进行基因组挖掘以识别高性能G8H酶.
- 进行了N-终端交换实验,以评估G8H酶功能.
- 结合工程酵母底盘,优化路径,并为增强生产选择G8H.
主要成果:
- 开发了一个简单的进化平台,以提高合成酵母中的日列产量.
- 与CrG8H相比,鉴定了具有优越的8-基醇生产能力的新型G8H酶.
- 证明了G8H N端对细胞活动的重要性.
- 在最终的工程菌株中,实现了30倍以上的8-基醇生产改善.
结论:
- 这项研究为优化酵母对8-基醇生物合成提供了一个强大的平台.
- 工程G8H酶和合成酵母底盘显著提高了前体的生产.
- 这项工作有助于可持续的微生物生产8-基醇及其衍生物用于制药应用.
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