对α分支有机酸生产途径的发现和工程
Michael R Blaisse1, Hongjun Dong1, Beverly Fu1
1Department of Chemistry, University of California, Berkeley , Berkeley, California 94720-1460, United States.
Journal of the American Chemical Society
|October 10, 2017
概括
研究人员设计了微生物菌株以产生分支酸,使用来自Ascaris suum的新型二氧化酶-二氧化酶对. 这一突破扩大了有价值的α分支化合物的生物合成能力.
科学领域:
- 生物技术
- 合成生物学
- 生物化学
背景情况:
- 基于细胞的合成可以通过发酵从可再生资源中产生小分子.
- 酶碳-碳键形成周期对于模块化生物合成至关重要,但面临基质限制.
- 酶启动合成,但对复杂分子的基质多样性有限.
研究的目的:
- 识别和描述用于产生分支碳酸的新酶.
- 设计微生物系统以有效生物合成α-甲基分支化合物.
- 扩大基于酶的合成途径的基质范围.
主要方法:
- 鉴定和生物化学表征来自Ascaris suum的二氧化酶对.
- 用大肠杆菌菌株进行分支酸的工程.
- 在体外和体内分析酶活性和途径选择性.
主要成果:
- 一种新型的酶-缩酶对选择性地使用propionyl-CoA产生α-甲基分支酸.
- 工程化大肠杆菌产生了性2-甲基-3-酸 (1.1 g L-1) 和分支酸 (1.12 g L-1).
- 确定降酶活性是α分支选择性的关键决定因素.
结论:
- 这些已识别的酶扩大了基于酶的生物合成途径的效用.
- 这项工作为聚合物和化学前体提供了α分支化合物的生物合成途径.
- 这种微生物可以有效地产生有价值的分支分子.
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