New breakthroughs in artificial optical enzyme research in the study of artificial optical enzymes!

Author:Huazhong University of Science Time:2022.09.27

September 21st

Huazhong University of Science and Technology

Team of the School of Chemistry and Chemical Technology Zhong Fangrui and Professor Wu Yuzhou

The paper cooperated with Professor Chen Xi of Northwest University

Enantioselective [2+2] -CyCLOADDITITINS With TRIPLLET Photoenzymes

Nature published in Nature

Wu Yuzhou, Zhong Fangrui, and Chen Xi are the joint communication authors of this article. Sun Ningning and Huang Jianjian of the School of Chemistry and Chemical Technology are the first authors of this article. Huazhong University of Science and Technology is the first author of the paper.

Enzymes are high -efficiency biocatalys formed by the long evolution of nature, but they are often only suitable for dedicated substrates and natural life chemical reactions, and it is difficult to meet the synthesis of social production of diverse functional chemicals. In recent years, with the development of synthetic biology theory and technology, the construction of artificial enzymes through artificial design and introducing non -natural activity centers in protein can greatly expand the catalytic reactionability of enzymes, thereby achieving more diverse non -natural organic chemistry Bio -catalytic synthesis. Although the number and types of biological enzymes formed by natural evolution are large and diverse, most of them are based on thermal chemical drive activation mechanisms. Natural optical enzymes that can be driven by optical are very scarce. At present, the optical enzymes that have been discovered are only a few types of primary chlorophyll acid ester enzymes related to photosynthesis, light crack enzymes that repair DNA damage, and fatty acid decarboxyrase. The photocatalyst and photocatalytic mechanism of synthetic chemical development are integrated into protein to build a new type of artificial optical enzyme, which can break the limit of natural enzyme thermal catalytic mechanism, fundamentally expand the type of reaction of biocatalyst, and provide the green biological manufacturing of important functional chemicals. New theory and technology.

On the other hand, handleness is closely related to life phenomena, which also significantly affects the performance of matter. The precise synthesis of hand -based molecules can provide core technical support for the development of medicine, pesticides, information and materials. Asymmetric catalysis is a very efficient way to prepare hand -to -hand. The research in this field has made great progress in the past half century. However, hand control of photochemical reactions in the excitation state is still a huge challenge.

"Triple Mental Opturase" artistic schematic diagram

In response to the above issues, Zhong Fangrui and Wu Yuzhou team proposed the concept of "triple -state optical enzyme". Through synthetic biology cutting -edge technology, a new type of artificial enzyme was developed, which provided an originality for hand -catalytic synthetic synthetic synthesis that stimulated the light reaction. Program. Based on the cross -disciplinary background of organic synthesis, genetic engineering, protein engineering, enzyme theoretical computing, and structural biology, the team has inserted the synthetic chemical development of the two -nozenone ketone -like optical agents through the genetic code sub -expansion technology to the hand that selected protein. In the sexual cavity, an artificial optical enzyme TPE containing non -natural catalytic catalytic centers is constructed. Due to the unique triple -state optical properties of dietthone, this optical enzyme has the non -natural function and action mechanism of energy transfer catalysis, which can catalyze the lesion transition from molecular base state to the exciting state. From the first -generation triple -state optical enzyme TPE1.0 constructed by chemical transformation, the team established a mutant library through four -wheel mutation and the formation of the amino acid residue and reaction empty structure of enzymes, completed the directional evolution of photocrangion, and finally obtained obtained Excellent mutant TPE4.0. The optical enzyme can efficiently catalyze the aura bonus reaction in the molecule of the derivatives. Obtain a single -handed heterogeneous more than 99%). The Chen Xi team clarified the single-crystal structure of the optical enzyme and the substrate mathematical composition through the X-ray analysis, and clarified that the excellent hand selectivity of the reaction comes from the multiple hydrogen bonds formed by the hydrogen bonding between the photoresistid agent and the surrounding key amino acid residues and the substrate. Weak key collaborate.

Triimite optical enzyme (TPE) catalytic energy transfer [2+2] halo bonus reaction diagram

This study shows that by combining the photocatalytic mechanism that transferred the triple -state energy transfer with the fine hyper molecular cavity of the protein, the artificial triple optical enzyme integrates the advantages of the high -efficiency reaction of chemical photocatalyst and the accurate selectivity of the biocity agent It provides effective means for hand -selective regulation for organic molecules to react, and also fundamentally expands the reactivity of enzyme catalytic. With the continuous improvement of the rational design capabilities of the computing artificial enzyme and the further development of the genetic code sub -expansion technology, more structured and unique chemical optical agents will be introduced into a new non -natural optical enzyme, thereby enriching the optical driving creature Catalytic function and application scope. Therefore, the concept of "triple -state optical enzyme" proposed by the research team is hoped that it is hoped to apply to more other types of asymmetric photocatalytic reactions.

The work was collaborated with Zhong Fangrui, Wu Yuzhou team with Chen Xi, Associate Professor Zhao Weining of Shenzhen University of Technology, and Professor Liao Rongzhen of Huazhong University of Science and Technology. They provided support from protein crystal analysis, protein spectrum, theoretical calculation and other support. The work was funded by the national key research and development plan synthetic biology project, the National Natural Science Foundation of China, and received the support of the instrument of the analysis and testing centers of Huazhong University of Science and Technology, the analysis and testing center of the School of Chemistry and Chemical and Chemical of the School of Chemistry and Chemical Engineering.

This paper is a breakthrough result of Wu Yuzhou and Zhong Fangrui's teams in the field of chemicals and organic synthetic chemical crossings. Wu Yuzhou has long been engaged in the research of the chemical modification and synthetic biology field of natural biomas such as protein and nucleic acids. The research direction includes the development and application of non -natural enzymes and protein materials, chemical modification of nucleic acid and nano -pharmaceutical materials. Related research results have published more than 80 papers in international authoritative journals such as Nature, Chemical Review, JACS, Angew Chem. Zhong Fangrui has long been engaged in the research of green bionic organic synthesis in the field of green bionic synthesis. The main directions include asymmetric catalytic and biocream catalysts. More than 50 papers have been published in journals such as Nature, JACS, and Angew CHEM. The School of Chemistry and Chemical Industry adheres to the concept of "accurate talents, sincere citation, scientific cultivation, and bold talent", based on the strategy of "strong talents", adheres to "exterior and internal cultivation, combination of quotation," Good talents, in politically trust, academic support, and management of burdens. By creating a healthy and upward academic ecology, free exploration academic atmosphere, the overall improvement of original innovation capabilities, high -level academic achievements compete for emergence. In 2019, the research results of Professor Xia Baoyu on the young talent Xia Baoyu were published in Science, and the college realized a breakthrough in the release of the papers in top CNS journals. After three years of research results, published in Nature. The growth of young talents has strongly supported the double first -class construction of chemical disciplines.