2023-07-28 カリフォルニア大学サンタバーバラ校(UCSB)
◆この新しい手法では、酵素的反応と光化学反応が協力してアミノ酸を生成し、立体選択的な化学反応を可能にします。従来の考えでは取り扱いが難しい自由基を、酵素的な中間分子が効果的に捕捉することで、効率的な反応が実現されています。
◆この研究により、新しい触媒反応の開発が可能になり、生物学と化学の両分野において重要な課題が解決される可能性が示されました。
<関連情報>
- https://www.news.ucsb.edu/2023/021153/new-synergistic-method-can-create-non-canonical-amino-acids-merging-synthetic
- https://www.science.org/doi/10.1126/science.adg2420
光レドックス-ピリドキサールラジカル生体触媒の相乗効果による立体選択的アミノ酸合成 Stereoselective amino acid synthesis by synergistic photoredox-pyridoxal radical biocatalysis
Lei Cheng,Dian Li,Binh Khanh Mai,Zhiyu Bo,Lida Cheng,Peng Liu, and Yang Yang
Science Published:27 Jul 2023
DOI:https://doi.org/10.1126/science.adg2420
Editor’s summary
Many enzymes have the ability to perform chemistry beyond the scope of their natural reactions when put together with reactive substrates. Adding light to the mix might be a strategy for broadening reactivity even further by generating radical species. Cheng et al. found that an engineered tryptophan synthase could function together with an organic photocatalyst to produce a range of noncanonical amino acid products, including those with a beta-methyl group, enantio- and diastereoselectively. The authors propose a mechanism in which a radical generated by the photocatalyst intercepts an aminoacrylate intermediate in a reaction cycle that partially parallels the natural reaction. —Michael A. Funk
Abstract
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.
