Wei Jianwei, Zhao Liang, Zhang Yu, Han Gang, He Cheng, Wang Chong, Duan Chunying
State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian 116024, P. R. China.
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, United States.
J Am Chem Soc. 2023 Mar 29;145(12):6719-6729. doi: 10.1021/jacs.2c12636. Epub 2023 Mar 14.
Semi-artificial approaches to solar-to-chemical conversion can achieve chemical transformations that are beyond the capability of natural enzymes, but face marked challenges to facilitate cascades, due to their inevitable need for cofactor shuttling and regeneration. Here, we report on an enzyme grafting strategy to build a metal-organic capsule-docking artificial enzyme (metal-organic-enzyme, MOE) that comprised the self-assembly of a cofactor-decorated capsule and the supramolecular enzyme-recognition features between the enzyme scaffold and the capsule to bypass cofactor shuttling and regeneration. The incorporated NADH mimics within the metal-organic capsule interacted with the imine intermediate that formed from the condensation of the amines and the dehydrogenation of alcohol substrates in the microenvironment to form complexes within the capsule and subsequently served as an -generated photoresponsive cofactor. Upon illumination, the photoresponsive cofactor facilitates efficient proton/electron transport between the inner space (supramolecular hydrogenation) and outer space (enzymatic dehydrogenation) of the capsule to dehydrogenize the alcohols and hydrogenize the imine intermediates, respectively, circumventing the conventionally complex multistep cofactor shuttling and regeneration. The semi-artificial enzyme endows the conversion of diverse types of alcohol to amine products in both aqueous/organic solutions and with high efficiency, offering a wide range of opportunities for sustainable and environmentally friendly biomanufacturing of commodity and fine chemicals.
太阳能到化学能转化的半人工方法能够实现天然酶无法完成的化学转化，但由于不可避免地需要辅因子穿梭和再生，在促进级联反应方面面临显著挑战。在此，我们报道了一种酶嫁接策略，用于构建一种金属有机胶囊对接人工酶（金属有机酶，MOE），它由辅因子修饰的胶囊自组装以及酶支架与胶囊之间的超分子酶识别特征组成，以绕过辅因子穿梭和再生。金属有机胶囊内掺入的NADH模拟物与微环境中胺缩合和醇底物脱氢形成的亚胺中间体相互作用，在胶囊内形成复合物，随后作为光生光响应辅因子。光照时，光响应辅因子促进质子/电子在胶囊内部空间（超分子氢化）和外部空间（酶促脱氢）之间的高效传输，分别使醇脱氢和亚胺中间体氢化，规避了传统上复杂的多步辅因子穿梭和再生过程。这种半人工酶能够在水相/有机溶液中高效地将多种类型的醇转化为胺产物，为商品和精细化学品的可持续和环境友好型生物制造提供了广泛的机会。
