一种单一的生物催化级,可以从化物或碳酸酸中获取多种L-氨衍生物
bioRxiv : the preprint server for biology
|December 16, 2024
概括
这项研究提出了一种新的生物催化级联,用于高效和可持续地合成各种非标准氨基酸 (nsAAs). 该方法利用天然酶来高产值生产有价值的L-氨衍生物,使这些化合物的获取更加民主化.
科学领域:
- 生物催化和酶工程 生物催化和酶工程
- 合成化学 合成化学
- 生物技术是生物技术.
背景情况:
- 非标准氨基酸 (nsAAs),特别是L-氨衍生物,在药物发现和合成中至关重要.
- 目前nsAAs的合成方法往往是低效的,enantioselective的,以及对环境的负担.
研究的目的:
- 开发一种多功能,高产量和可扩展的生物催化方法,用于合成各种nsAAs.
- 为了克服传统有机合成路线的局限性,用于合性nsAA生产.
主要方法:
- 利用皮里多克萨尔5'-酸盐 (PLP) 依赖酶 (L-threonine转酶,氨酸脱水酶,氨基转移酶) 的广泛基质特异性.
- 使用天然酶从化物合成L-phenylalanine衍生物构建一个单生物催化级联.
- 整合一个碳酸减少酶模块,用于从碳酸合成碳酸.
- 开发一种基于 lysate 的路径,用于准备性规模的合成.
主要成果:
- 在温和的水性条件下从化物中获得18种不同的L-phenylalanine衍生物的高产合成.
- 从碳酸酸中证明了nsAA衍生物的成功生物合成.
- 建立了一个可扩展的,基于lysate的4-formyl-L-phenylalanine的生产.
结论:
- 开发的生物催化级联为nsAA合成提供了一个高效,多功能和可扩展的途径.
- 这种方法有可能显著降低制造成本,并提高有价值的nsAAs的可访问性.
- 这项研究扩大了PLP依赖酶在合成化学中的实用性.
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