Departments of Chemistry and Materials Science & Engineering , University of Utah , 315 South 1400 East, Room 2020 , Salt Lake City , Utah 84112 , United States.
J Am Chem Soc. 2019 Mar 27;141(12):4963-4971. doi: 10.1021/jacs.9b00147. Epub 2019 Mar 13.
Enantiomerically pure chiral amines are of increasing value in the preparation of bioactive compounds, pharmaceuticals, and agrochemicals. ω-Transaminase (ω-TA) is an ideal catalyst for asymmetric amination because of its excellent enantioselectivity and wide substrate scope. To shift the equilibrium of reactions catalyzed by ω-TA to the side of the amine product, an upgraded N fixation system based on bioelectrocatalysis was developed to realize the conversion from N to chiral amine intermediates. The produced NH was in situ reacted with l-alanine dehydrogenase to generate alanine with NADH as a coenzyme. ω-TA transferred the amino group from alanine to ketone substrates and finally produced the desired chiral amine intermediates. The cathode of the upgraded N fixation system supplied enough reducing power to synchronously realize the regeneration of reduced methyl viologen (MV) and NADH for the nitrogenase and l-alanine dehydrogenase. The coproduct, pyruvate, was consumed by l-alanine dehydrogenase to regenerate alanine and push the equilibrium to the side of amine. After 10 h of reaction, the concentration of 1-methyl-3-phenylpropylamine achieved 0.54 mM with the 27.6% highest faradaic efficiency and >99% enantiomeric excess (ee). Because of the wide substrate scope and excellent enantioselectivity of ω-TA, the upgraded N fixation system has great potential to produce a variety of chiral amine intermediates for pharmaceuticals and other applications.
对映体纯手性胺在生物活性化合物、药物和农用化学品的制备中越来越有价值。ω-转氨酶（ω-TA）因其出色的对映选择性和广泛的底物范围，是不对称胺化反应的理想催化剂。为了将 ω-TA 催化的反应平衡向胺产物一侧移动，开发了一种基于生物电化学的升级氮固定系统，以实现从 N 到手性胺中间体的转化。产生的 NH 与 l-丙氨酸脱氢酶原位反应，以 NADH 为辅酶生成丙氨酸。ω-TA 将氨基从丙氨酸转移到酮底物上，最终产生所需的手性胺中间体。升级氮固定系统的阴极提供了足够的还原力，以同步实现固氮酶和 l-丙氨酸脱氢酶还原甲基紫精（MV）和 NADH 的再生。副产物丙酮酸被 l-丙氨酸脱氢酶消耗，以丙氨酸再生并推动平衡向胺侧移动。反应 10 小时后，1-甲基-3-苯基丙胺的浓度达到 0.54 mM，最高法拉第效率为 27.6%，对映体过量（ee）大于 99%。由于 ω-TA 具有广泛的底物范围和出色的对映选择性，升级氮固定系统具有很大的潜力，可以用于生产各种手性胺中间体，用于药物和其他应用。
