在工程化埃舍里奇亚大肠杆菌中新兴合成1-乙化诺

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Yaping Mao^1,2,3, Jiangming Zhu^1,2,3, Qian Zhang^1,2

¹CAS-Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai 200032, China.

Synthetic and systems biotechnology

|December 9, 2024

概括

工程化埃舍里希亚大肠杆菌现在产生1 - 乙化素 (PIA) 前体,使得医学上重要的乙化素类化合物的高产量. 这种微生物细胞工厂方法推进了PIA生物合成和大规模生产.

科学领域:

代谢工程是代谢工程.
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:

甲基化物 (PIA) 是有价值的天然产品,具有重要的药用应用.
在PIA异质生产的挑战源于不完整的生物合成途径知识和缺乏优化的微生物宿主.
1-phenylethylisoquinoline支架是PIA合成的关键前体.

研究的目的:

在工程Escherichia coli中为1-phenylethylisoquinoline前体建立一个新的生物合成途径.
通过酶优化和宿主工程来提高前体产量.
为了使微生物生产具有高附加值的PIA相关类化合物.

主要方法:

在大肠杆菌中为1-phenylethylisoquinoline生物合成的人工八种酶途径的构建.
通过酶选,辅因子再生和位点定向突变发生,优化中间4-二二甲产量.
将一个修改后的多巴胺通路集成到一个富含铁素,缺少减少酶的大肠杆菌菌株中.

主要成果:

成功设计了大肠杆菌,使其能够对1-phenylethylisoquinoline前体进行 de novo 生物合成.
在5L发酵器中获得了402.58mg/L的1-phenylethylisoquinoline的高产量.
证明了将途径工程与宿主菌株优化相结合的有效性.

结论:

这项研究展示了一个强大的工程大肠杆菌细胞工厂,用于高效的1-phenylethylisoquinoline生产.
开发的人工通路和优化的主机为大规模制造PIA提供了基础.
微生物PIA生物合成的进步为更广泛地获得这些医学上重要的化合物铺平了道路.

关键词:

1 - - 乙化诺氨酸.新生生物合成的新生生物合成埃舍里希亚大肠杆菌 (Escherichia coli) 是一个大肠杆菌.甲基化素类化物.降解酶可以减少.

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