{"title":"","authors":"Qiang Li, George Yan and Dionisios G. Vlachos*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9,"journal":{"name":"ACS Catalysis ","volume":"15 12","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":11.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscatal.5c00874","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wonchul Park, Jongsu Noh, Hongmin An, Jooyoung Kim and Dong Young Chung*,
{"title":"","authors":"Wonchul Park, Jongsu Noh, Hongmin An, Jooyoung Kim and Dong Young Chung*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9,"journal":{"name":"ACS Catalysis ","volume":"15 12","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":11.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscatal.5c01749","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ACS Catalysis Pub Date : 2025-06-20DOI: 10.1021/acscatal.5c01532
Yinghui Feng, Xin Yan, Mingzhe Ma, Ruyi Chen, Chuanxi Zhang, Yalong Cong, Bohuan Fang, Chunchi Chen, Longhai Dai, Hao Li, Haiming Jiang, Hong Sun, Hao Wei, Reyting Guo, Bei Gao, John Z. H. Zhang, Lujia Zhang
{"title":"Aqualigase: A Star Enzyme for One-Step Peptide Bond Dehydration Condensation in a Nature Aqueous Phase","authors":"Yinghui Feng, Xin Yan, Mingzhe Ma, Ruyi Chen, Chuanxi Zhang, Yalong Cong, Bohuan Fang, Chunchi Chen, Longhai Dai, Hao Li, Haiming Jiang, Hong Sun, Hao Wei, Reyting Guo, Bei Gao, John Z. H. Zhang, Lujia Zhang","doi":"10.1021/acscatal.5c01532","DOIUrl":"https://doi.org/10.1021/acscatal.5c01532","url":null,"abstract":"One-step amine–carboxyl dehydration condensation in cells (100% aqueous phase) is the most efficient and sustainable natural method for peptide and protein synthesis. However, most peptide ligases need modifications of substrates at the C- or N-terminal. To create this ligase, we engineered a “water-shielded” reaction chamber in protease subtilisin-P225A through precise polarization calculation using our self-developed PPC force field, thereby converting the hydrolysis reaction to a ligation reaction. We marked the first success and achieved 12 monomutants at first-round mutagenesis. The combined mutant P225A/N62L/S63L/Y217L/N218F with the highest activity was named Aqualigase. The X-ray structural and HDX-MS analysis confirmed a 20%–50% reduction in proton exchange and 50% elimination of water from the active site, demonstrating the success of the “water-shielding effect”. With Aqualigase/N158E, we successfully achieved the one-step synthesis of teriparatide, addressing the long-standing challenges in long-chain peptide or protein ligation. Notably, Aqualigase was also able to catalyze dealcoholizing ligation, transamidation, and esterification reactions. Its suitability for the length, size, and even the N- or C-terminal sequence composition of peptides or protein provides a huge scope for in situ protein conjunction in cells and peptide synthesis in industry.","PeriodicalId":9,"journal":{"name":"ACS Catalysis ","volume":"25 1","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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