设计一种生物合成途径,以生产 (+) - 布雷维亚胺 A 和 B
Casandra P Sandoval Hurtado1,2, Samantha P Kelly1,2, Vikram Shende1,2
1Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, United States.
概括
工程微生物产生复杂的双循环[2.2.2]二氧化 (BDO) 化物,简化了获得这些强大的天然产品的途径. 这种生物合成方法产生了有价值的化合物,提高了效率和多重选择性.
科学领域:
- 合成生物学 合成生物学
- 自然产品的生物合成.
- 代谢工程是代谢工程.
背景情况:
- 带有双环[2.2.2]二氧化 (BDO) 核的二基托皮佩拉 (DKPs) 是生物活性天然产品.
- 目前用于DKP生产的方法产生的数量很少,缺乏二元体选择性.
研究的目的:
- 开发一种简化和高效的方法来生产含有BDO的DKPs.
- 在大肠杆菌中设计一种新的生物合成途径,用于复杂的类化合物合成.
主要方法:
- 使用来自不同生物体的基因设计了六种酶生物合成途径.
- 经过工程 *Escherichia coli* 来表达该途径并产生 (-) - 脱烯胺 E.
- 优化NADPH池以提高产品标题.
主要成果:
- 获得了5.3mg/L的 (-) - 脱烯维亚胺 E 的产量标位,增加到20.6mg/L.
- 合成的 (+) - 简胺A和B,产量为70%,二聚体比为94:6.
- 证明了生物合成工程和化学合成的成功结合.
结论:
- 工程设计的大肠杆菌可以有效地产生复杂的醇化物.
- 这种方法克服了天然产品提取和传统合成的局限性.
- 提供了一个可扩展的平台,用于访问含有有价值的BDO的DKPs.
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