Stereoselective amino acid synthesis by synergistic photoredox-pyridoxal radical biocatalysis

• 成果类型: Article
• 署名作者: Cheng, Lei; Li, Dian; Mai, Binh Khanh; Bo, Zhiyu; Cheng, Lida; Liu, Peng; Yang, Yang
• 署名单位: University of California System; University of California Santa Barbara; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of California System; University of California Santa Barbara
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-14090
• DOI: 10.1126/science.adg2420
• 发表日期: 2023-07-28
• 页码: 444-451
• 关键词: asymmetric-synthesis; directed evolution; enzymes; pathways; toolbox; carbene; access

摘要

Developing synthetically useful enzymatic reactions that are not known in biochemistry and organic chemistry is an important challenge in biocatalysis. Through the synergistic merger of photoredox catalysis and pyridoxal 5'-phosphate (PLP) biocatalysis, we developed a pyridoxal radical biocatalysis approach to prepare valuable noncanonical amino acids, including those bearing a stereochemical dyad or triad, without the need for protecting groups. Using engineered PLP enzymes, either enantiomeric product could be produced in a biocatalyst-controlled fashion. Synergistic photoredox-pyridoxal radical biocatalysis represents a powerful platform with which to discover previously unknown catalytic reactions and to tame radical intermediates for asymmetric catalysis.