在l-伊索瓦林生物合成中形成阿齐里丁的α-甲酸依赖氧基酶的表征
Lu Zhou1,2, Takayoshi Awakawa1,2, Richiro Ushimaru1,3
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Organic letters
|January 16, 2024
概括
研究人员发现了Tolypocladium膨胀酶如何产生l-isovaline. 一个特定的酶突变改变了立体选择性,影响了最终的d-异氨酸产品,为生物合成途径提供了洞察力.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 分子生物学分子生物学
背景情况:
- 伊索瓦林是一种非蛋白质生成氨基酸,具有潜在的应用.
- 在Tolypocladium inflatum中,l-异氨酸的生物合成途径涉及特定的酶.
研究的目的:
- 为了阐明通过TqaLFM-ti从Tolypocladium inflatum中的l-isovaline的体外生物合成.
- 描述了α-甲酸依赖氧化酶TqaL-ti的立体选择性.
- 为了研究特定突变对酶立体选择性的影响.
主要方法:
- 在体外生化分析TqaLFM-ti.
- 酶动力学和产品的特征.
- TqaL-ti. 的局部定向突变发生.
主要成果:
- TqaL-ti从l-单氨酸中产生 (2S,3S) -3-乙基-3-甲基拉齐里丁-2-碳酸,与同类药物相比显示出明显的立体选择性.
- 在TqaL-ti中I295的一个单一突变逆转了它的立体选择性.
- TqaFM-ti将阿齐里丁中间体转化为d-异氨酸,其立体化学是由TqaL产品决定的.
结论:
- 由TqaL产生的亚齐里丁中间体的立体化学决定了异氨酸的最终立体化学.
- 通过向突变发生的酶工程可以精确地控制氨基酸生物合成中的立体选择性.
- 这项研究为理解和操纵非蛋白质性氨基酸生产提供了基础.
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