Reshaping the Substrate Binding Pocket of β-Amino Acid Dehydrogenase for the Synthesis of Aromatic β-Amino Acids

被引:0
|
作者
Liu, Na [1 ]
Feng, Jinhui [1 ]
Chen, Xi [1 ]
Luo, Yuyang [1 ,2 ]
Lv, Tong [1 ]
Wu, Qiaqing [1 ]
Zhu, Dunming [1 ]
机构
[1] Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Natl Engn Res Ctr Ind Enzymes, Tianjin Engn Res Ctr Biocatalyt Technol,Key Lab En, Tianjin 300308, Peoples R China
[2] Tianjin Univ Sci & Technol, Sch Biotechnol, State Key Lab Food Nutr & Safety, Key Lab Ind Fermentat Microbiol,Minist Educ, Tianjin 300457, Peoples R China
基金
国家重点研发计划; 中国国家自然科学基金;
关键词
CATALYTIC ASYMMETRIC-SYNTHESIS; PEPTIDE;
D O I
10.1021/acs.orglett.3c03366
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
By reshaping the substrate-binding pocket of beta-amino acid dehydrogenase (beta-AADH), some variants were obtained with up to 2560-fold enhanced activity toward the model substrates (S)-beta-homophenylalanine and (R)-beta-phenylalanine. A few aromatic beta-amino acids were prepared with >99% ee and high isolated yields via either kinetic resolution of racemates or reductive amination of the corresponding beta-keto acids. This work expands the catalytic capability of beta-AADHs and highlights their practical application in the synthesis of pharmaceutically relevant beta-amino acids.
引用
收藏
页码:8469 / 8473
页数:5
相关论文
共 50 条
  • [1] Computational Redesign of the Substrate Binding Pocket of Glutamate Dehydrogenase for Efficient Synthesis of Noncanonical L-Amino Acids
    Wang, Ziyuan
    Zhou, Haisheng
    Yu, Haoran
    Pu, Zhongji
    Xu, Jinling
    Zhang, Hongyu
    Wu, Jianping
    Yang, Lirong
    ACS CATALYSIS, 2022, 12 (21) : 13619 - 13629
  • [2] Substrate-Specific Engineering of Amino Acid Dehydrogenase Superfamily for Synthesis of a Variety of Chiral Amines and Amino Acids
    Zhou, Feng
    Xu, Yan
    Nie, Yao
    Mu, Xiaoqing
    CATALYSTS, 2022, 12 (04)
  • [3] Efficient enzymatic synthesis of α-keto acids by redesigned substrate-binding pocket of the L-amino acid deaminase (PmiLAAD)
    Wu, Licheng
    Guo, Xiaolei
    Wu, Gaobing
    Liu, Pengfu
    Liu, Ziduo
    ENZYME AND MICROBIAL TECHNOLOGY, 2020, 132 (132)
  • [4] Structure and function of Plasmodium falciparum malate dehydrogenase: Role of critical amino acids in co-substrate binding pocket
    Pradhan, Anupam
    Tripathi, Abhai K.
    Desai, Prashant V.
    Mukherjee, Prasenjit K.
    Avery, Mitchell A.
    Walker, Larry A.
    Tekwani, Babu L.
    BIOCHIMIE, 2009, 91 (11-12) : 1509 - 1517
  • [5] Development of β-Amino Acid Dehydrogenase for the Synthesis of β-Amino Acids via Reductive Amination of β-Keto Acids
    Zhang, Dalong
    Chen, Xi
    Zhang, Rui
    Yao, Peiyuan
    Wu, Qiaqing
    Zhu, Dunming
    ACS CATALYSIS, 2015, 5 (04): : 2220 - 2224
  • [6] Reshaping amino acids
    Qin, Jingyang
    Teskey, Christopher J.
    NATURE SYNTHESIS, 2024, 3 (12): : 1451 - 1452
  • [7] Synthesis of aromatic amino acids V
    Houben, J
    Freund, R
    BERICHTE DER DEUTSCHEN CHEMISCHEN GESELLSCHAFT, 1913, 46 : 3833 - 3839
  • [8] Synthesis of Photoreactive Aromatic α-Amino Acids and Effective Hydrogen-Deuterium Exchange for Aromatic α-Amino Acids
    Hashimoto, Makoto
    Murai, Yuta
    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN, 2014, 72 (04) : 360 - 369
  • [9] Reshaping an Enzyme Binding Pocket for Enhanced and Inverted Stereoselectivity: Use of Smallest Amino Acid Alphabets in Directed Evolution
    Sun, Zhoutong
    Lonsdale, Richard
    Kong, Xu-Dong
    Xu, Jian-He
    Zhou, Jiahai
    Reetz, Manfred T.
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2015, 54 (42) : 12410 - 12415
  • [10] Identification of amino acids in the binding pocket of the human KDEL receptor
    Scheel, AA
    Pelham, HRB
    JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (04) : 2467 - 2472