为了高效地生产体,工程体
Xiaoxu Lin1, Xingwang Xu1, Dongxu Zhang1
1State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Journal of agricultural and food chemistry
|August 22, 2025
概括
链杆菌宿主被设计为可扩展的化物生产,克服了传统宿主的局限性. 这项研究通过优化代谢途径实现了包括氧化衍生物在内的四种复杂类的高产量.
科学领域:
- 代谢工程
- 合成生物学
- 自然产品生物合成
背景情况:
- 类植物具有重要的农业和治疗潜力,但由于自然丰度低和复杂的氧化定制,它们面临生产挑战.
- 传统的微生物宿主往往缺乏必要的酶机制,特别是细胞P450,以有效地产生复杂的衍生物.
研究的目的:
- 为可扩展的结构复杂的化物生产开发替代微生物底盘.
- 利用Streptomyces的生物合成能力来增强类合成和氧化定制.
主要方法:
- 设计了两个Streptomyces宿主作为替代生产底盘.
- 采用了EcoMine策略来识别和组装含有MEP通路基因的TriMEP磁带.
- 优化培养基和利用强大的基因表达促进剂.
主要成果:
- 在震动瓶培养中实现了四种特类的高水平生产,其中包括三种氧化产品.
- 报告的产量包括 (-) -epi-α-bisabolol (237 ± 14 mg/L),ent-(13Z) -isocupressic 酸 (173 ± 14 mg/L),ent-(13E) -isocupressic 酸 (209 ± 20 mg/L) 和ent-atiserenoic 酸 (325 ± 17 mg/L).
- 在工程化Streptomyces宿主中证明了成功的P450氧化调整.
结论:
- 链杆菌作为一个坚固且未被充分利用的微生物底盘,用于可持续生产复杂的类.
- 开发的代谢工程策略可以获得有价值的氧化衍生物.
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