在工业Streptomyces avermitilis菌株中理性地提高多拉美丁的生产
Fujun Dang1, Qingyu Xu1, Zhongjun Qin1
1Key Laboratory of Synthetic Biology, The Center of Excellent Plant Molecular Sciences, The Chinese Academy of Sciences, Shanghai 200032, China.
Bioengineering (Basel, Switzerland)
|June 28, 2023
概括
改造的Streptomyces avermitilis使得多拉克丁的产量增加了260%以上. 这涉及去除竞争的多基基路径和过度表达一个关键的CoA连接酶基因,为这种抗寄生虫剂提供了一种具有成本效益的方法.
科学领域:
- 微生物生物技术 微生物生物技术
- 合成生物学 合成生物学
- 自然产品生物合成 自然产品生物合成
背景情况:
- 阿维美克丁 (AVM) 是一种由Streptomyces avermitilis.产生的强效抗寄生虫宏类药物.
- 多拉美克丁是一种关键的AVM衍生物,在兽医中至关重要.
- 竞争的多基化物生物合成途径可以限制多拉克的产量.
研究的目的:
- 为了增强Streptomyces avermitilis中的多拉克丁生产.
- 为了设计一种微生物菌株,提高抗寄生虫剂的产量.
- 开发一种具有成本效益的多拉克丁制造方法.
主要方法:
- 在Streptomyces avermitilis的基因工程.
- 删除了三个多基酸合成酶 (PKS) 基因集群.
- 编码CoA结合酶的fadD17基因的过度表达.
主要成果:
- 改造的DM223菌株实现了大约723mg/L的多拉克丁产量.
- 这与原始菌株DM203 (大约260%) 相比,相当于大约260%的显著增加. 280 毫克/升). 在这种情况下,
- 成功地破坏了竞争的途径,并增强了前体供应.
结论:
- 一个合理的代谢工程策略显著改善了多拉克的产量.
- 消除路径和增强前体路径的结合方法是有效的.
- 这项工作为具有成本效益的多拉amectin工业生产提供了基础.
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