设计一种大肠杆菌菌株以提高从pinocembrin中提取的黄类素的生产
Erik K R Hanko1, Christopher J Robinson1, Sahara Bhanot1
1Manchester Institute of Biotechnology, Faculty of Science and Engineering, University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
Microbial cell factories
|November 19, 2024
概括
这项研究将大肠杆菌 (Escherichia coli) 改造为产生高产量的皮诺布林,这是一个关键的黄类中间体. 增强的微生物生产皮诺布林及其衍生物,如素和素,为类生物合成开辟了新的途径.
科学领域:
- 代谢工程是代谢工程.
- 合成生物学 合成生物学
- 生物化学 生物化学
背景情况:
- 黄类化合物是具有显著药理价值的植物性化合物.
- 皮诺坎布林是黄类生物合成的关键中间体,但微生物的生产是有限的.
- 开发高效的微生物细胞工厂用于各种类黄仍然是一个挑战.
研究的目的:
- 增强微生物产生的皮诺布林及其衍生物.
- 为了设计大肠杆菌作为一个细胞工厂,用于类生物合成.
- 为了克服当前异质黄酸生产的局限性.
主要方法:
- 对大肠杆菌进行基因工程,以优化前体供应 (氨酸和马洛尼尔-CoA).
- 对关键生物合成步骤 (FNS,7-OMT,F3H/FLS) 的各种酶候选物的选.
- 使用已建立的应变工程策略和组合图书馆.
主要成果:
- 在没有前体补充的情况下,在大肠杆菌中实现了353 ± 19 mg/L的皮诺坎布林产量.
- 使用Petroselinum crispum FNSI生产了82 ± 5 mg/L的.
- 产生了153 ± 10毫克/升的皮诺斯特罗宾与欧卡利普斯尼蒂达皮诺森布林7-OMT.
- 通过使用Glycine max F3H/FLS.获得12.6 ± 1.8 mg/L的pinobanksin.
- 通过组合方法达到18.2 ± 5.3 mg/L的加兰.
结论:
- 通过底盘工程和酶查,成功增加了微生物产生的平诺和衍生物.
- 工程化的大肠杆菌平台显示出生产多种类型的黄类药物的巨大潜力.
- 未来的工作重点是辅助因子供应和毒性减轻,可能进一步提高产量,并使更广泛的应用.
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