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在Saccharomyces cerevisiae中重新编程碳分区用于化过度生产.

Jian Li1,2,3, Honghao Li1,2,3, Xiaoran Dai1,2,3

  • 1Frontiers Science Center for Synthetic Biology (Ministry of Education), School of Synthetic Biology and Biomanufacturing, Tianjin University, Tianjin 300072, China.

ACS synthetic biology
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概括

微生物产生的沙利德化物被增强的工程中心代谢和细胞壁合成. 这一策略克服了UDP-葡萄糖的竞争,为这个有价值的糖化物实现了创纪录的40.46g/L标位.

关键词:
在UDP-葡萄糖通路上.细胞壁工程 细胞壁工程辅助因子工程是指工程中的一个因素.代谢工程是代谢工程.沙利德化物是什么

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科学领域:

  • 生物技术和合成生物学
  • 代谢工程是代谢工程.
  • 自然产品生物合成 自然产品生物合成

背景情况:

  • 沙利德化物是一种有价值的植物性糖化物,具有显著的营养药和制药潜力.
  • 微生物的沙利德化物生产受限于细胞壁合成和沙利德化物形成之间对UDP-葡萄糖 (UDPG) 的竞争.

研究的目的:

  • 设计一个高产量的微生物细胞工厂,用于增强沙利德化物生产.
  • 为了克服UDP-葡萄糖 (UDPG) 在糖化物合成中的竞争瓶.

主要方法:

  • 使用硫胺二酸盐 (ThDP) 再生重新连接中央新陈代谢,以增加铁醇前体的产生.
  • 引入了一种糖系转移酶 (RrU8GT33),用于将铁醇转化为沙利德化物.
  • 通过UGP1和PGM1过度表达,增强了UDP-葡萄糖 (UDPG) 的可用性.
  • 通过调节FKS1表达来重定向碳流,实现了细胞壁工程.

主要成果:

  • 在生物反应器发酵中达到40.46g/L的破纪录的salidroside标位.
  • 它的生产率为0.24g/Lh,产量为0.27g/g葡萄糖.
  • 通过综合工程策略,成功地将生长压力与沙利德化物合成需求脱.

结论:

  • 辅助因子和细胞壁工程是优化微生物糖化物生产的有效策略.
  • 开发了一种可扩展的方法,用于工业生产高价值的天然糖化物,如沙利德化物.