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一个多酶级联,用于从L-tyrosine有效地生产D-p-hydroxyphenylglycine

Xu Tan^1,2, Sheng Zhang³, Wei Song^1,2

¹School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, China.

Bioresources and bioprocessing

|April 23, 2024

概括

一种新型的四种酶途径有效地从L-氨酸中产生D-p-基甘氨酸 (D-HPG). 蛋白质工程增强了一个关键的酶,促进了用于抗生素和精细化学品的D-HPG生产.

科学领域:

生物催化剂是一种生物催化剂.
酶工程是指酶工程的工程.
代谢工程是代谢工程.

背景情况:

D-p-hydroxyphenylglycine (D-HPG) 是制药和精细化学品的关键中间体.
目前的D-HPG生产方法在效率和成本效益方面存在局限性.

研究的目的:

从L-tyrosine开发一个高效的体内酶途径,用于从L-tyrosine产生D-HPG.
通过蛋白质工程来克服D-HPG合成途径中的速度限制步骤.

主要方法:

在体内重建一个四种酶级联路径.
使用机理导向策略识别和设计中亚氨基酸脱酶 (CgDAPDH).
优化酶变体以提高活性和化物转移效率.

主要成果:

工程CgDAPDH变体 (CgDAPDH^{BC621/D120S/W144S/I169P}) 显示显著增加的特定活性.
在24小时内从50g/L L-tyrosine中获得了42.69g/L的D-HPG标位.
在3L发酵器中,证明了高转化率 (92.5%),孤立产量 (71.5%) 和反体过量 (>99%).

结论:

开发的四种酶级联途径为工业D-HPG生产提供了一种高效的生物催化方法.
蛋白质工程策略可以有效地增强酶活性并改善途径性能.
这种方法为生产有价值的化学中间体提供了一个可持续且具有成本效益的替代方案.

关键词:

d-p-hydroxyphenylglycine是什么意思?d-p-hydroxyphenylglycine是什么意思?d-p-hydroxyphenylglycine是什么意思?d-p-hydroxyphenylglycine是什么意思?d-p-hydroxyphenylglycine是什么意思?d-p-hydroxyphenylglycine是什么意思?l-铁氨酸是一种介质-二氨基基胺酸脱酶.化物转移距离的距离蛋白质工程是一种蛋白质工程.

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