Xu Weihua, Mou Kaihao, Lu Zhenyu, Kang Xiuwen, Guo Yue, Ding Bei, Chen Zhirong, Wang Zhiguo, Wu Qi
Center of Chemistry for Frontier Technologies, Department of Chemistry, Zijingang Campus, Zhejiang University, Hangzhou, 310058, China.
Center for Ultrafast Science and Technology, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
Angew Chem Int Ed Engl. 2024 Dec 20;63(52):e202412862. doi: 10.1002/anie.202412862.
In the field of biocatalysis, discovering novel reactivity from known enzymes has been a longstanding challenge. Fatty acid photo-decarboxylase from Chlorella variabilis (CvFAP) has drawn considerable attention as a promising photoenzyme with potential green chemistry applications; however, its non-natural reactivity has rarely been exploited to date. Herein we report a non-natural reductive dehalogenation (deacetoxylation) reactivity of CvFAP inspired by its natural oxidative decarboxylation process, enabling the stereoselective synthesis of a series of chiral α-substituted tetralones with high yields (up to 99 %) and e.r. values (up to 99 : 1). Mechanistic studies demonstrated that the native photoenzyme catalyzed the reductive dehalogenation via a novel mechanism involving oxidized state (FAD)/semiquinone state (FAD) redox pair and an electron transfer (ET)/proton transfer (PT) process of radical termination, distinct from the previous reports. To our knowledge, this study represents a new example of CvFAP promiscuity, and thus expands the reactivity repertoire of CvFAP and highlights the versatility of CvFAP in asymmetric synthesis.
在生物催化领域，从已知酶中发现新的反应活性一直是一项长期挑战。来自小球藻的脂肪酸光脱羧酶（CvFAP）作为一种具有潜在绿色化学应用前景的光酶，已引起了相当大的关注；然而，其非天然反应活性迄今为止很少被开发利用。在此，我们报道了受CvFAP天然氧化脱羧过程启发的一种非天然还原脱卤（脱乙酰氧基化）反应活性，能够以高产率（高达99%）和对映体过量值（高达99:1）立体选择性地合成一系列手性α-取代四氢萘酮。机理研究表明，天然光酶通过一种涉及氧化态（FAD）/半醌态（FAD）氧化还原对以及自由基终止的电子转移（ET）/质子转移（PT）过程的新机制催化还原脱卤，这与之前的报道不同。据我们所知，这项研究代表了CvFAP多功能性的一个新例子，从而扩展了CvFAP的反应活性范围，并突出了CvFAP在不对称合成中的多功能性。
