Li Min, Zhang Yan, Fu Kai, Deng Zhiwei, Yuan Zhenbo, Luo Zhengshan, Rao Yijian
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, P. R. China.
School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, P. R. China.
J Am Chem Soc. 2025 Apr 23;147(16):13190-13199. doi: 10.1021/jacs.4c16521. Epub 2025 Apr 12.
The creation of enzymes with abiological abilities offers exciting opportunities to access new-to-nature biocatalysis beyond that found in nature. Here, we repurpose a novel protein scaffold, CTB10, as an artificial photoenzyme through genetic code expansion. It enables catalytic deracemization of cyclopropane, a process that remains inaccessible to traditional biocatalysis due to its thermodynamically unfavorable nature. Following structural optimization through directed evolution, a broad substrate scope with high enantioselectivities is achieved. Furthermore, the crystal structure of the CTB10-based photoenzyme-substrate complex well demonstrates how the catalytic chiral cavity is sculpted to promote efficient and selective light-enabled deracemization. Therefore, this study unlocks the potential for achieving challenging deracemization through biocatalysis.
创造具有非天然能力的酶为实现超越自然界中发现的新型生物催化提供了令人兴奋的机会。在这里，我们通过遗传密码扩展将一种新型蛋白质支架CTB10重新用作人工光酶。它能够实现环丙烷的催化去消旋化，由于其热力学性质不利，传统生物催化无法实现这一过程。通过定向进化进行结构优化后，实现了具有高对映选择性的广泛底物范围。此外，基于CTB10的光酶-底物复合物的晶体结构很好地展示了催化手性腔是如何塑造的，以促进高效和选择性的光驱动去消旋化。因此，这项研究开启了通过生物催化实现具有挑战性的去消旋化的潜力。
