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在酵母中复制和优化Marmesin生物合成途径

Zhaoxin Wang^1,2, Ying Zhou³, Yuefei Wang^1,2

¹State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

ACS synthetic biology

|September 28, 2023

概括

工程酵母可以生产marmesin,一种植物防御化合物. 这项研究实现了27.7 mg/L的标位,为绿色生产法库马林铺平了道路.

科学领域:

代谢工程是代谢工程.
合成生物学合成生物学
生物技术是生物技术.

背景情况:

马尔梅辛是一种具有多样化的生物活动的关键植物防御化合物.
马尔梅因的高效生产对于其制药应用至关重要.

研究的目的:

为了设计一种Saccharomyces cerevisiae底盘,用于马氏体的新生物合成.
优化新陈代谢途径和酶活性,以提高马氏素产量.

主要方法:

在酵母中重建了marmesin生物合成途径.
通过引入大肠杆菌ppsA.引入工程芳香氨基酸 (AAA) 生物合成.
过度表达了抗反的ARO4和ARO7,并删除了埃里希路径基因 (ARO10,PDC5,PDC6).
通过切断跨膜域和增加基因拷贝数量,优化了贝利费龙6 - 双甲基基转移酶 (U6DT) 和马尔梅林合成酶 (MS).

主要成果:

改善了前体的可用性,并将代谢流向氨酸.
从埃里希路径减少了副产品的形成.
在工程酵母菌株MU5.5中达到27.7mg/L的marmesin标位.

结论:

成功建立了用于马尔梅斯生产的酵母菌株.
证明了绿色和大规模合成子胺的潜力.
工程菌株作为制药生产的基础.

关键词:

这种植物是Saccharomyces cerevisiae.在新生物合成的新生生物合成.富拉诺库马林是一种.马尔梅辛 (marmesin) 是一种水力发电机.马尔梅辛合成酶是什么

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