化学原理驱动的光生物不对称催化研究进展

Recent advances in chemically driven enantioselective photobiocatalysis

手性选择性的调控一直是合成化学的重要研究主题。酶是绿色、高选择性的天然手性催化剂,但在绿色生物合成中的应用受限于进化形成的分子结构和催化机制,光催化通过捕获光子能量实现底物分子的化学键活化,是引发自由基反应的重要策略,融合光化学和酶的光生物催化正成为不对称催化合成的新兴合成工具。利用蛋白质改造、定向进化等先进分子生物学技术,基于光化学的化学原理挖掘辅酶的非天然催化功能,探索光催化剂与酶的协同耦合作用新模式,理性设计人为定义功能的人工光酶,能突破天然酶催化的底物谱和反应类型,有效弥补天然光酶的稀缺性,拓展生物催化的化学边界和合成空间。本文综述了化学原理驱动光生物催化不对称反应的最新研究进展,依据光和酶之间的耦合模式和催化机制,将文献分为外源光催化剂与天然酶耦合、电子供体-受体复合物激发驱动的光酶催化、辅酶直接光氧化还原和光酶能量转移催化四种不同类型,分别详细探讨其分子活化机制和立体化学调控的化学原理。此外,本文也对光生物不对称催化存在的辅酶类型单调、催化效率低等挑战进行了总结,并从天然酶库的深度挖掘、人工光酶类型的拓展、酶的从头设计和全细胞催化等角度展望了未来的发展方向,通过化学和生物融合实现高价值功能分子的绿色生物制造,推动合成化学的可持续发展。

Stereochemical control is an important long-standing research topic in synthetic chemistry.Enzymes,as green and highly selective natural chiral catalysts,face constrains in synthetic applications due to their evolution-defined molecular structure and catalytic mechanism.Photocatalysis represents an important strategy to initiate free radical reactions by capturing photon energy to activate the chemical bonds of substrate molecules.As an emerging synthetic tool for asymmetric synthesis,photobiocatalysis merges the advantages of photochemistry and enzyme.Unfortunately,photoenzymes are rather rare in nature.Thus far photoenzymes identified are DNA photolyases,lightdependent protochlorophyllide reductases and blue light-responsive algal photodecarboxylases.Utilization of advanced molecular biotechnologies such as protein engineering and directed evolution under the guidance of chemical mechanisms of photocatalysis enables us to explore unknown photocatalytic functions of natural coenzymes,synergize photocatalysts and enzymes,and rationally design artificial photoenzyme with defined functions.The past few years have witnessed remarkable advances in these aspects,significantly surpassing the spectrum of substrates and reactions of enzyme catalysis,compensating for the scarcity of natural photo-enzymes and expanding the chemical boundaries and synthetic space of biocatalysis.This review summarizes the latest research progress in chemically-driven photoenzymatic asymmetric reactions.Based on their merging modes,the review categorizes the integration of light and enzyme into four classes:coupling of exogenous photocatalysts and native enzymes,photobiocatalysis driven by excitation of electron donor-acceptor complex,direct photoredox catalysis by coenzymes,and energy transfer photobiocatalysis.The chemical mechanism of bond activation by photocatalysis and synergistic control of stereoselectivity by enzyme in these photobiocatalytic systems are discussed in detail.In the end of this review,we also delineate the present challenges of asymmetric photobiocatalysis including the monotonicity of native photoactive cofactors and low catalytic efficiency for abiological reactions.This review also proposes future directions from the perspectives of new natural enzyme mining,expansion of artificial photoenzymes,enzyme de novo design,and wholecell catalysis,which are anticipated to foster green bio-manufacturing of high-value functional molecules through the fusion of chemistry and biology and push forward the sustainable development of synthetic chemistry.