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科学家发现一种酶促Alder-ene反应
2020-10-04 22:47

美国加州大学洛杉矶分校Yi Tang等研究人员合作发现一种酶促Alder-ene反应。2020年9月30日,国际知名学术期刊《自然》发表了这一成果。

研究人员发现了两组同源的周环素酶,它们催化不同的反应:一组催化是生物学上未知的Alder-ene反应;另一组催化立体选择性hetero-Diels–Alder 反应。在计算研究的指导下,研究人员揭示了观察到的反应性差异,并设计了突变酶来逆转从Alder-ene到异Diels-Alder的周向选择性,反之亦然。体外生化特征、计算研究、酶共晶体结构和突变研究的结合说明了在几乎相同的活性位点上如何实现高区域选择性和周选择性。
 
据介绍,化学研究中的一项持续挑战是设计能够选择复杂分子反应结果的催化剂。化学家依靠有机催化剂或过渡金属催化剂来控制立体选择性、区域选择性和周向选择性(周环反应之间的选择性)。大自然通过多种酶来实现这些类型的选择性,例如最近发现的周环酶-一种催化周环反应的酶家族。最典型的酶促环周反应是环加成反应,很难合理地实现观察到的选择性。
 
附:英文原文

Title: An enzymatic Alder-ene reaction

Author: Masao Ohashi, Cooper S. Jamieson, Yujuan Cai, Dan Tan, Daiki Kanayama, Man-Cheng Tang, Sarah M. Anthony, Jason V. Chari, Joyann S. Barber, Elias Picazo, Thomas B. Kakule, Shugeng Cao, Neil K. Garg, Jiahai Zhou, K. N. Houk, Yi Tang

Issue&Volume: 2020-09-30

Abstract: An ongoing challenge in chemical research is to design catalysts that select the outcomes of the reactions of complex molecules. Chemists rely on organocatalysts or transition metal catalysts to control stereoselectivity, regioselectivity and periselectivity (selectivity among possible pericyclic reactions). Nature achieves these types of selectivity with a variety of enzymes such as the recently discovered pericyclases—a family of enzymes that catalyse pericyclic reactions1. Most characterized enzymatic pericyclic reactions have been cycloadditions, and it has been difficult to rationalize how the observed selectivities are achieved2,3,4,5,6,7,8,9,10,11,12,13. Here we report the discovery of two homologous groups of pericyclases that catalyse distinct reactions: one group catalyses an Alder-ene reaction that was, to our knowledge, previously unknown in biology; the second catalyses a stereoselective hetero-Diels–Alder reaction. Guided by computational studies, we have rationalized the observed differences in reactivities and designed mutant enzymes that reverse periselectivities from Alder-ene to hetero-Diels–Alder and vice versa. A combination of in vitro biochemical characterizations, computational studies, enzyme co-crystal structures, and mutational studies illustrate how high regioselectivity and periselectivity are achieved in nearly identical active sites.

DOI: 10.1038/s41586-020-2743-5

Source: https://www.nature.com/articles/s41586-020-2743-5

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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