| Title: |
Photosensitizer Repositioning Affords an Enantiocomplementary Enzyme for [2 + 2]‐Cycloadditions. |
| Authors: |
Sun, Chuanjie; Kohn, Anna R.; Smithson, Ross; Hardy, Florence J.; Trimble, Jonathan S.; Cao, Yuanxin; Johannissen, Linus O.; Hay, Sam; Crawshaw, Rebecca; Green, Anthony P. |
| Source: |
Angewandte Chemie; 8/25/2025, Vol. 137 Issue 35, p1-6, 6p |
| Subject Terms: |
Enzymes; Chirality; Regioselectivity (Chemistry); Protein engineering; Stereoselective reactions; Photosensitizers; Molecules; Ring formation (Chemistry) |
| Abstract: |
The combination of genetic code expansion and directed evolution has recently given rise to enantioselective photoenzymes for [2 + 2]‐cycloadditions of quinolone and indole derivatives. However, the enzymes reported to date only allow access to one enantiomeric series of the strained cyclobutane products. Here, guided by a crystal structure of our previously engineered enzyme EnT1.3, we show how judicious repositioning of the genetically programmed benzophenone photosensitizer affords an enantiocomplementary [2 + 2]‐cyclase, CEnT1.0. Following directed evolution, a proficient and oxygen‐tolerant photoenzyme (CEnT1.4) emerged that promotes [2 + 2]‐cycloadditions of a quinolone derivative with exquisite enantiocontrol (99% e.e.) and substantially enhanced regioselectivity compared with EnT1.3 (r.r. 62:1 vs. 9:1). Structural analysis of CEnT1.4, coupled with molecular dynamic simulations, reveals a well‐sculpted active site pocket that pre‐organises the substrate for regio‐ and enantioselective catalysis. This study highlights the versatility offered by genetically programmed (photo)catalytic elements when developing enzymes for altered stereochemical outcomes. [ABSTRACT FROM AUTHOR] |
| : |
Copyright of Angewandte Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |