A review on enzyme-catalyzed synthesis of chiral amino acids

WANG Ziyuan; YANG Lirong; WU Jianping; ZHENG Wenlong

doi:10.12211/2096-8280.2024-015

您当前的位置：

首页 >

文章列表页 >

A review on enzyme-catalyzed synthesis of chiral amino acids

Invited Review | 更新时间：2025-04-11

- A review on enzyme-catalyzed synthesis of chiral amino acids
- Synthetic Biology Journal Vol. 5, Issue 6, Pages: 1319-1349(2024)
- 作者机构：
  
  1.浙江大学杭州国际科创中心，生物与分子智造研究院，浙江杭州 311215
  2.浙江大学化学工程与生物工程学院，浙江杭州 310058
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2024-015
  CLC： Q814
- Received：04 February 2024，
  
  Revised：2024-05-16，
  
  Published：31 December 2024
- 稿件说明：
移动端阅览
王子渊，杨立荣，吴坚平，郑文隆. 酶促合成手性氨基酸的研究进展［J］. 合成生物学， 2024， 5（6）： 1319-1349

WANG Ziyuan， YANG Lirong， WU Jianping， ZHENG Wenlong. A review on enzyme-catalyzed synthesis of chiral amino acids［J］. Synthetic Biology Journal， 2024， 5（6）： 1319-1349
王子渊，杨立荣，吴坚平，郑文隆. 酶促合成手性氨基酸的研究进展［J］. 合成生物学， 2024， 5（6）： 1319-1349 DOI： 10.12211/2096-8280.2024-015.

WANG Ziyuan， YANG Lirong， WU Jianping， ZHENG Wenlong. A review on enzyme-catalyzed synthesis of chiral amino acids［J］. Synthetic Biology Journal， 2024， 5（6）： 1319-1349 DOI： 10.12211/2096-8280.2024-015.

摘要

手性氨基酸是一类重要的高价值化学品，广泛应用于食品、医药、化工、农药等多个领域。手性氨基酸常用的制备方法可以分为四类，包括化学合成、蛋白质水解、发酵和酶促合成。其中，酶促合成手性氨基酸以其反应条件温和、立体选择性高、步骤简单、应用范围广等优势备受关注。近年来，得益于生物信息学和蛋白质工程等技术的快速发展，大量性能优异的酶制剂被开发，并成功应用于多种手性氨基酸的制备。本文重点综述了酶促不对称合成和去消旋化合成两种路径在手性氨基酸合成中的应用，包括关键酶制剂氨基酸脱氢酶、转氨酶、氨裂解酶、醛缩酶、氨基酸氧化酶、氨基酸脱氨酶等的开发与改造，及其在草铵膦、叔亮氨酸、西格列汀中间体等高价值手性氨基酸合成中的应用。同时，总结了酶促合成手性氨基酸领域面临的主要困境，如关键酶元件缺乏，以及野生酶非对映体选择性低、底物谱窄、催化活性低、稳定性差、反应条件局限等。最后，展望了自动化实验装置、机器学习和人工智能等前沿技术在酶改造领域的应用，以及通过反应器设计和反应过程控制，开发更为高效和环境友好的催化工艺，推动酶促合成手性氨基酸技术更广泛的工业应用。

Abstract

Chiral amino acids represent a crucial class of chiral building blocks with significant value in food

medicine

chemical industry

and agriculture. The market scale of pharmaceuticals

pesticides

food

and chemical industries relying on chiral amino acids is substantial and has been attracting increasing attention. The pursuit of efficient

environmentally friendly

and cost-effective synthesis of chiral amino acids has long been a goal for scientists. Commonly used preparation methods for chiral amino acids fall into four following categories: protein hydrolysis

fermentation

chemical synthesis

and enzyme-catalyzed synthesis. Among these

enzyme-catalyzed synthesis has demonstrated great potential due to its mild reaction conditions

high stereo-selectivity

simplicity of steps

and wide application range. In recent years

with the rapid development of bioinfo

rmatics

protein engineering

and computational biology

there has been an increasing number of high-performance enzyme preparations developed

leading to a steady increase in the diversity of enzymes and the gradual diversification of catalyzed reactions

further promoting the wide application of enzyme-catalyzed synthesis of chiral amino acids. The enzyme-catalyzed synthesis of chiral amino acids can be categorized into three groups: asymmetric synthesis

deracemization synthesis

and kinetic resolution. Kinetic resolution

due to its theoretical yield of only 50% and low atom economy

is not suitable for industrial applications. In contrast

asymmetric synthesis and deracemization synthesis with theoretical yield of 100% find wider industrial application. This article reviews the application of enzymatic asymmetric synthesis and deracemization synthesis in the synthesis of chiral amino acids. It includes the development and modification of key enzyme such as amino acid dehydrogenase

transaminase

ammonia lyase

aldolase

amino acid oxidase

and amino acid deaminase

as well as their application in the synthesis of high-value chiral amino acids such as phosphinothricin

tert

-leucine

and intermediate of sitagliptin. Additionally

it summarizes the main challenges faced in the field of enzymatic synthesis of chiral amino acids

such as the lack of key enzyme components

and low enantioselectivity

narrow substrate spectra

low catalytic activity

poor stability

limited reaction conditions of wild-type enzymes. Finally

it looks ahead to the application of cutting-edge technologies such as automated experimental devices

machine learning

and artificial intelligence in the field of enzyme modification

as well as the development of more efficient and environmentally friendly catalytic processes through reactor design and reaction process control. These endeavors collectively aim to facilitate the broader industrial application of enzymatic synthesis for chiral amino acids.

关键词

Keywords

references

BOMMARIUS A S , SCHWARM M , STINGL K , et al . Synthesis and use of enantiomerically pure tert -leucine [J ] . Tetrahedron: Asymmetry , 1995 , 6 ( 12 ): 2851 - 2888 .

SHIN J S , KIM B G . Transaminase-catalyzed asymmetric synthesis of L-2-aminobutyric acid from achiral reactants [J ] . Biotechnology Letters , 2009 , 31 ( 10 ): 1595 - 1599 .

ZHU L , TAO R S , WANG Y , et al . Removal of L-alanine from the production of L-2-aminobutyric acid by introduction of alanine racemase and D-amino acid oxidase [J ] . Applied Microbiology and Biotechnology , 2011 , 90 ( 3 ): 903 - 910 .

TAO R S , JIANG Y , ZHU F Y , et al . A one-pot system for production of L-2-aminobutyric acid from L-threonine by L-threonine deaminase and a NADH-regeneration system based on L-leucine dehydrogenase and formate dehydrogenase [J ] . Biotechnology Letters , 2014 , 36 ( 4 ): 835 - 841 .

BAO Z X , SUN Y , RAI K , et al . The promising indicators of the thermal and mechanical properties of collagen from bass and tilapia: synergistic effects of hydroxyproline and cysteine [J ] . Biomaterials Science , 2018 , 6 ( 11 ): 3042 - 3052 .

ZHOU H S , MENG L J , YIN X J , et al . Biocatalytic asymmetric synthesis of L-phosphinothricin using a one-pot three enzyme system and a continuous substrate fed-batch strategy [J ] . Applied Catalysis A: General , 2020 , 589 : 117239 .

MANANDHAR M , CHUN E , ROMESBERG F E . Genetic code expansion: inception, development, commercialization [J ] . Journal of the American Chemical Society , 2021 , 143 ( 13 ): 4859 - 4878 .

DU Y H , LI L , ZHENG Y , et al . Incorporation of non-canonical amino acids into antimicrobial peptides: advances, challenges, and perspectives [J ] . Applied and Environmental Microbiology , 2022 , 88 ( 23 ): e0161722 .

UGWUMBA I N , OZAWA K , XU Z Q , et al . Improving a natural enzyme activity through incorporation of unnatural amino acids [J ] . Journal of the American Chemical Society , 2011 , 133 ( 2 ): 326 - 333 .

WILKINSON H C , DALBY P A . Fine-tuning the activity and stability of an evolved enzyme active-site through noncanonical amino-acids [J ] . The FEBS Journal , 2021 , 288 ( 6 ): 1935 - 1955 .

WANG L X , ZHU W J , GAO Z , et al . Biosynthetic L- tert -leucine using Escherichia coli co-expressing a novel NADH-dependent leucine dehydrogenase and a formate dehydrogenase [J ] . Electronic Journal of Biotechnology , 2020 , 47 : 83 - 88 .

ZHOU F , MU X Q , NIE Y , et al . Enhanced catalytic efficiency and coenzyme affinity of leucine dehydrogenase by comprehensive screening strategy for L- tert -leucine synthesis [J ] . Applied Microbiology and Biotechnology , 2021 , 105 ( 9 ): 3625 - 3634 .

SAVILE C K , JANEY J M , MUNDORFF E C , et al . Biocatalytic asymmetric synthesis of chiral amines from ketones applied to sitagliptin manufacture [J ] . Science , 2010 , 329 ( 5989 ): 305 - 309 .

杨立荣 , 周海胜 , 居述云 , 等 . 一种生物酶法去消旋化制备L‑草铵膦的方法 : CN201710834958.4 [P ] . 2017-09-15 .

YANG L R , ZHOU H S , JU S Y , et al . A method of enzymatic racemization for preparing L-phosphinothricin : CN201710834958.4 [P ] . 2017-09-15 .

CAO C H , GONG H , DONG Y , et al . Enzyme cascade for biocatalytic deracemization of D,L-phosphinothricin [J ] . Journal of Biotechnology , 2021 , 325 : 372 - 379 .

TANG C D , SHI H L , JIA Y Y , et al . High level and enantioselective production of L-phenylglycine from racemic mandelic acid by e ngineered Escherichia coli using response surface methodology [J ] . Enzyme and Microbial Technology , 2020 , 136 : 109513 .

HEINKS T , PAULUS J , KOOPMEINERS S , et al . Recombinant L-amino acid oxidase with broad substrate spectrum for co-substrate recycling in ( S )-selective transaminase-catalyzed kinetic resolutions [J ] . ChemBioChem , 2022 , 23 ( 16 ): e202200329 .

WEGNER U , MATTHES F , VON WIRÉN N , et al . Enhancing a Sphaerobacter thermophilus ω-transaminase for kinetic resolution of β- and γ-amino acids [J ] . AMB Express , 2023 , 13 ( 1 ): 117 .

ZHOU F , XU Y , NIE Y , et al . Substrate-specific engineering of amino acid dehydrogenase superfamily for synthesis of a variety of chiral amines and amino acids [J ] . Catalysts , 2022 , 12 ( 4 ): 380 .

TOMITA T , YIN L L , NAKAMURA S , et al . Crystal structure of the 2-iminoglutarate-bound complex of glutamate dehydrogenase from Corynebacterium glutamicum [J ] . FEBS Letters , 2017 , 591 ( 11 ): 1611 - 1622 .

OLIVEIRA T , PANJIKAR S , CARRIGAN J B , et al . Crystal structure of NAD + -dependent Peptoniphilus asaccharolyticus glutamate dehydrogenase reveals determinants of cofactor specificity [J ] . Journal of Structural Biology , 2012 , 177 ( 2 ): 543 - 552 .

YIN X J , LIU Y Y , MENG L J , et al . Semi-rational hinge engineering: modulating the conformational transformation of glutamate dehydrogenase for enhanced reductive amination activity towards non-natural substrates [J ] . Catalysis Science & Technology , 2020 , 10 ( 10 ): 3376 - 3386 .

SON H F , KIM I K , KIM K J . Structural insights into domain movement and cofactor specificity of glutamate dehydrogenase from Corynebacterium glutamicum [J ] . Biochemical and Biophysical Research Communications , 2015 , 459 ( 3 ): 387 - 392 .

PRAKASH P , PUNEKAR N S , BHAUMIK P . Structural basis for the catalytic mechanism and α-ketoglutarate cooperativity of glutamate dehydrogenase [J ] . The Journal of Biological Chemistry , 2018 , 293 ( 17 ): 6241 - 6258 .

WU T , WANG Y M , ZHANG N X , et al . Reshaping substrate-binding pocket of leucine dehydrogenase for bidirectionally accessing structurally diverse substrates [J ] . ACS Catalysis , 2023 , 13 ( 1 ): 158 - 168 .

WANG Z Y , QU H J , LI W Q , et al . Semi-rational design of diaminopimelate dehydrogenase from Symbiobacterium thermophilum improved its activity toward hydroxypyruvate for D-serine synthesis [J ] . Catalysts , 2023 , 13 ( 3 ): 576 .

LIU N , WU L , FENG J H , et al . Crystal structures and catalytic mechanism of L-erythro-3,5-diaminohexanoate dehydrogenase and rational engineering for asymmetric synthesis of β-amino acids [J ] . Angewandte Chemie International Edition , 2021 , 60 ( 18 ): 10203 - 10210 .

WANG Z Y , ZHOU H S , YU H R , et al . Computational redesign of the substrate binding pocket of glutamate dehydrogenase for efficient synthesis of noncanonical L-amino acids [J ] . ACS Catalysis , 2022 , 12 ( 21 ): 13619 - 13629 .

YIN X J , ZENG Y J , CHEN J , et al . Combined active pocket and hinge region engineering to develop an NADPH-dependent phenylglycine dehydrogenase [J ] . Bioorganic Chemistry , 2022 , 120 : 105601 .

LUO W , ZHU J , ZHAO Y Z , et al . Cloning and expression of a novel leucine dehydrogenase: characterization and L- tert -leucine production [J ] . Frontiers in Bioengineering and Biotechnology , 2020 , 8 : 186 .

MENG X Q , YANG L , LIU Y , et al . Identification and rational engineering of a high substrate-tolerant leucine dehydrogenase effective for the synthesis of L- tert -leucine [J ] . ChemCatChem , 2021 , 13 ( 14 ): 3340 - 3349 .

LIAO L X , ZHANG Y H , WANG Y L , et al . Construction and characterization of a novel glucose dehydrogenase-leucine dehydrogenase fusion enzyme for the biosynthesis of L- tert -leucine [J ] . Microbial Cell Factories , 2021 , 20 ( 1 ): 3 .

LIU Y , ZHONG X Z , LUO Z , et al . The identification of a robust leucine dehydrogenase from a directed soil metagenome for efficient synthesis of L-2-aminobutyric acid [J ] . Biotechnology Journal , 2023 , 18 ( 8 ): e2200590 .

付妍 , 张君轩 , 付雪蓉 , 等 . 三酶级联催化L-苏氨酸生产L-2-氨基丁酸 [J ] . 生物工程学报 , 2020 , 36 ( 4 ): 782 - 791 .

FU Y , ZHANG J X , FU X R , et al . Production of L-2-aminobutyric acid from L-threonine using a trienzyme cascade [J ] . Chinese Journal of Biotechnology , 2020 , 36 ( 4 ): 782 - 791 .

CHENG F , LI H , ZHANG K , et al . Tuning amino acid dehydrogenases with featured sequences for L-phosphinothricin synthesis by reductive amination [J ] . Journal of Biotechnology , 2020 , 312 : 35 - 43 .

TANG C D , ZHANG Z H , SHI H L , et al . Directed evolution of formate dehydrogenase and its application in the biosynthesis of L-phenylglycine from phenylglyoxylic acid [J ] . Molecular Catalysis , 2021 , 513 : 111666 .

MENG X Q , LIU Y , YANG L , et al . Rational identification of a high catalytic efficiency leucine dehydrogenase and process development for efficient synthesis of l-phenylglycine [J ] . Biotechnology Journal , 2023 , 18 ( 5 ): e2200465 .

SCHNEIDER G , KÄCK H , LINDQVIST Y . The manifold of vitamin B 6 dependent enzymes [J ] . Structure , 2000 , 8 ( 1 ): R1 - R6 .

ELIOT A C , KIRSCH J F . Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations [J ] . Annual Review of Biochemistry , 2004 , 73 : 383 - 415 .

ROCHA J F , PINA A F , SOUSA S F , et al . PLP-dependent enzymes as important biocatalysts for the pharmaceutical, chemical and food industries: a structural and mechanistic perspective [J ] . Catalysis Science & Technology , 2019 , 9 ( 18 ): 4864 - 4876 .

BEZSUDNOVA E Y , POPOV V O , BOYKO K M . Structural insight into the substrate specificity of PLP fold type Ⅳ transaminases [J ] . Applied Microbiology and Biotechnology , 2020 , 104 ( 6 ): 2343 - 2357 .

SHIN J S , KIM B G . Exploring the active site of amine: pyruvate aminotransferase on the basis of the substrate structure-reactivity relationship: how the enzyme controls substrate specificity and stereoselectivity [J ] . The Journal of Organic Chemistry , 2002 , 67 ( 9 ): 2848 - 2853 .

MATHEW S , YUN H . ω-Transaminases for the production of optically pure amines and unnatural amino acids [J ] . ACS Catalysis , 2012 , 2 ( 6 ): 993 - 1001 .

SHILOVA S A , MATYUTA I O , KHRENOVA M G , et al . In search for structural targets for engineering D-amino acid transaminase: modulation of pH optimum and substrate specificity [J ] . The Biochemical Journal , 2023 , 480 ( 16 ): 1267 - 1284 .

SHILOVA S A , MATYUTA I O , PETROVA E S , et al . Expanded substrate specificity in D-amino acid transaminases: a case study of transaminase from Blastococcus saxobsidens [J ] . International Journal of Molecular Sciences , 2023 , 24 ( 22 ): 16194 .

VOSS M , XIANG C , ESQUE J , et al . Creation of ( R )-amine transaminase activity within an α-amino acid transaminase scaffold [J ] . ACS Chemical Biology , 2020 , 15 ( 2 ): 416 - 424 .

MOORE J C , RODRIGUEZ-GRANILLO A , CRESPO A , et al . “Site and mutation”-specific predictions enable minimal directed evolution libraries [J ] . ACS Synthetic Biology , 2018 , 7 ( 7 ): 1730 - 1741 .

JIA D X , PENG C , LI J L , et al . Redesign of ( R )-omega-transaminase and its application for synthesizing amino acids with bulky side chain [J ] . Applied Biochemistry and Biotechnology , 2021 , 193 ( 11 ): 3624 - 3640 .

CHENG F , CHEN X L , XIANG C , et al . Fluorescence-based high-throughput screening system for R -ω-transaminase engineering and its substrate scope extension [J ] . Applied Microbiology and Biotechnology , 2020 , 104 ( 7 ): 2999 - 3009 .

VOSS M , DAS D , GENZ M , et al . In silico based engineering approach to improve transaminases for the conversion of bulky substrates [J ] . ACS Catalysis , 2018 , 8 ( 12 ): 11524 - 11533 .

WANG Y G , FENG J H , DONG W Y , et al . Improving catalytic activity and reversing enantio-specificity of ω-transaminase by semi-rational engineering en route to chiral bulky β-amino esters [J ] . ChemCatChem , 2021 , 13 ( 15 ): 3396 - 3400 .

WALTON C J W , THIEBAUT F , BRUNZELLE J S , et al . Structural determinants of the stereoinverting activity of Pseudomonas stutzeri D-phenylglycine aminotransferase [J ] . Biochemistry , 2018 , 57 ( 37 ): 5437 - 5446 .

NOVICK S J , DELLAS N , GARCIA R , et al . Engineering an amine transaminase for the efficient production of a chiral sacubitril precursor [J ] . ACS Catalysis , 2021 , 11 ( 6 ): 3762 - 3770 .

ST-JACQUES A D , EYAHPAISE M È C , CHICA R A . Computational design of multisubstrate enzyme specificity [J ] . ACS Catalysis , 2019 , 9 ( 6 ): 5480 - 5485 .

JEON H , PAGAR A D , KANG H , et al . Creation of a ( R )-β- transaminase by directed evolution of D-amino acid aminotransferase [J ] . ACS Catalysis , 2022 , 12 ( 21 ): 13207 - 13214 .

LAND H , CAMPILLO-BROCAL J C , SVEDENDAHL HUMBLE M , et al . B-factor guided proline substitutions in Chromobacterium violaceum amine transaminase: evaluation of the proline rule as a method for enzyme stabilization [J ] . ChemBioChem , 2019 , 20 ( 10 ): 1297 - 1304 .

XIE Z H , ZHAI L X , MENG D , et al . Improving the catalytic thermostability of Bacillus altitudinis W3 ω-transaminase by proline substitutions [J ] . 3 Biotech , 2020 , 10 ( 7 ): 323 .

MARCHINI V , BENÍTEZ-MATEOS A I , HUTTER S L , et al . Fusion of formate dehydrogenase and alanine dehydrogenase as an amino donor regenerating system coupled to transaminases [J ] . ChemBioChem , 2022 , 23 ( 21 ): e202200428 .

KELEFIOTIS-STRATIDAKIS P , TYRIKOS-ERGAS T , PAVLIDIS I V . The challenge of using isopropylamine as an amine donor in transaminase catalysed reactions [J ] . Organic & Biomolecular Chemistry , 2019 , 17 ( 7 ): 1634 - 1642 .

DAWOOD A W H , WEIß M S , SCHULZ C , et al . Isopropylamine as amine donor in transaminase-catalyzed reactions: better acceptance through reaction and enzyme engineering [J ] . ChemCatChem , 2018 , 10 ( 18 ): 3943 - 3949 .

KHOBRAGADE T P , SARAK S , PAGAR A D , et al . Synthesis of sitagliptin intermediate by a multi-enzymatic cascade system using lipase and transaminase with benzylamine as an amino donor [J ] . Frontiers in Bioengineering and Biotechnology , 2021 , 9 : 757062 .

ZHENG X X , CUI Y L , LI T , et al . Biochemical and structural characterization of a highly active branched-chain amino acid aminotransferase from Pseudomonas sp. for efficient biosynthesis of chiral amino acids [J ] . Applied Microbiology and Biotechnology , 2019 , 103 ( 19 ): 8051 - 8062 .

LUO W , HU J G , LU J P , et al . One pot cascade synthesis of L-2-aminobutyric acid employing ω-transaminase from Paracoccus pantotrophus [J ] . Molecular Catalysis , 2021 , 515 : 111890 .

YU J H , LI J , CAO S Y , et al . Chemoenzymatic synthesis of L-3,4-dimethoxyphenyl-alanine and its analogues using aspartate aminotransferase as a key catalyst [J ] . Catalysis Communications , 2019 , 120 : 28 - 32 .

KHOBRAGADE T P , YU S , JUNG H , et al . Promoter engineering-mediated Tuning of esterase and transaminase expression for the chemoenzymatic synthesis of sitagliptin phosphate at the kilogram-scale [J ] . Biotechnology & Bioengineering , 2021 , 118 ( 8 ): 3263 - 3268 .

KHOBRAGADE T P , PAGAR A D , GIRI P , et al . Biocatalytic cascade for synthesis of sitagliptin intermediate employing coupled transaminase [J ] . Biotechnology and Bioprocess Engineering , 2023 , 28 ( 2 ): 300 - 309 .

RODA S , FERNANDEZ-LOPEZ L , BENEDENS M , et al . A plurizyme with transaminase and hydrolase activity catalyzes cascade reactions [J ] . Angewandte Chemie International Edition , 2022 , 61 ( 37 ): e202207344 .

KHOBRAGADE T P , GIRI P , PAGAR A D , et al . Dual-function transaminases with hybrid nanoflower for the production of value-added chemicals from biobased levulinic acid [J ] . Frontiers in Bioengineering and Biotechnology , 2023 , 11 : 1280464 .

ZHANG Z J , CAI R F , XU J H . Characterization of a new nitrilase from Hoeflea phototrophica DFL-43 for a two-step one-pot synthesis of ( S )-β-amino acids [J ] . Applied Microbiology and Biotechnology , 2018 , 102 ( 14 ): 6047 - 6056 .

PARMEGGIANI F , WEISE N J , AHMED S T , et al . Synthetic and therapeutic applications of ammonia-lyases and aminomutases [J ] . Chemical Reviews , 2018 , 118 ( 1 ): 73 - 118 .

POPPE L , PAIZS C , KOVÁCS K , et al . Preparation of unnatural amino acids with ammonia-lyases and 2,3-aminomutases [J ] . Methods in Molecular Biology , 2012 , 794 : 3 - 19 .

FIBRIANSAH G , VEETIL V P , POELARENDS G J , et al . Structural basis for the catalytic mechanism of aspartate ammonia lyase [J ] . Biochemistry , 2011 , 50 ( 27 ): 6053 - 6062 .

LEVY C W , BUCKLEY P A , SEDELNIKOVA S , et al . Insights into enzyme evolution revealed by the structure of methylaspartate ammonia lyase [J ] . Structure , 2002 , 10 ( 1 ): 105 - 113 .

VIOLA R E . The ammonia-lyases: enzymes that use a wide range of approaches to catalyze the same type of reaction [J ] . Critical Reviews in Biochemistry and Molecular Biology , 2019 , 54 ( 6 ): 467 - 483 .

WALKER K D , KLETTKE K , AKIYAMA T , et al . Cloning, heterologous expression, and characterization of a phenylalanine aminomutase involved in taxol biosynthesis [J ] . Journal of Biological Chemistry , 2004 , 279 ( 52 ): 53947 - 53954 .

KALKREUTER E , SHEN B . MIO-containing aminomutases for α- to β-amino acids [J ] . Trends in Chemistry , 2022 , 4 ( 1 ): 91 - 92 .

ATTANAYAKE G , WALTER T , WALKER K D . Understanding which residues of the active site and loop structure of a tyrosine aminomutase define its mutase and lyase activities [J ] . Biochemistry , 2018 , 57 ( 25 ): 3503 - 3514 .

BATA Z , MOLNÁR Z , MADARAS E , et al . Substrate tunnel engineering aided by X-ray crystallography and functional dynamics swaps the function of MIO-enzymes [J ] . ACS Catalysis , 2021 , 11 ( 8 ): 4538 - 4549 .

CHESTERS C , WILDING M , GOODALL M , et al . Thermal bifunctionality of bacterial phenylalanine aminomutase and ammonia lyase enzymes [J ] . Angewandte Chemie International Edition , 2012 , 51 ( 18 ): 4344 - 4348 .

AHMED S T , PARMEGGIANI F , WEISE N J , et al . Engineered ammonia lyases for the production of challenging electron-rich L-phenylalanines [J ] . ACS Catalysis , 2018 , 8 ( 4 ): 3129 - 3132 .

HARDEGGER L A , BENEY P , BIXEL D , et al . Toward a scalable synthesis and process for EMA401, part Ⅲ: Using an engineered phenylalanine ammonia lyase enzyme to synthesize a non-natural phenylalanine derivative [J ] . Organic Process Research & Development , 2020 , 24 ( 9 ): 1763 - 1771 .

BOROS K , MOISĂ M E , NAGY C L , et al . Robust, site-specifically immobilized phenylalanine ammonia-lyases for the enantioselective ammonia addition of cinnamic acids [J ] . Catalysis Science & Technology , 2021 , 11 ( 16 ): 5553 - 5563 .

CUI Y L , WANG Y H , TIAN W Y , et al . Development of a versatile and efficient C—N lyase platform for asymmetric hydroamination via computational enzyme redesign [J ] . Nature Catalysis , 2021 , 4 ( 5 ): 364 - 373 .

BRACK Y , SUN C H , YI D , et al . Exploring the substrate switch motif of aromatic ammonia lyases [J ] . ChemBioChem , 2023 , 24 ( 23 ): e202300584 .

ABIDIN M Z , SARAVANAN T , ZHANG J L , et al . Modular enzymatic cascade synthesis of vitamin B 5 and its derivatives [J ] . Chemistry , 2018 , 24 ( 66 ): 17434 - 17438 .

NI Z F , XU P , ZONG M H , et al . Structure-guided protein engineering of ammonia lyase for efficient synthesis of sterically bulky unnatural amino acids [J ] . Bioresources and Bioprocessing , 2021 , 8 ( 1 ): 103 .

SZYMANSKI W , WU B , WEINER B , et al . Phenylalanine aminomutase-catalyzed addition of ammonia to substituted cinnamic acids: a route to enantiopure alpha- and beta-amino acids [J ] . The Journal of Organic Chemistry , 2009 , 74 ( 23 ): 9152 - 9157 .

WU B , SZYMAŃSKI W , WYBENGA G G , et al . Mechanism-inspired engineering of phenylalanine aminomutase for enhanced β-regioselective asymmetric amination of cinnamates [J ] . Angewandte Chemie International Edition , 2012 , 51 ( 2 ): 482 - 486 .

AHMED S T , PARMEGGIANI F , WEISE N J , et al . Synthesis of enantiomerically pure ring-substituted L-pyridylalanines by biocatalytic hydroamination [J ] . Organic Letters , 2016 , 18 ( 21 ): 5468 - 5471 .

DÜCKERS N , BAER K , SIMON S , et al . Threonine aldolases—screening, properties and applications in the synthesis of non-proteinogenic β-hydroxy-α-amino acids [J ] . Applied Microbiology and Biotechnology , 2010 , 88 ( 2 ): 409 - 424 .

DI SALVO M L , REMESH S G , VIVOLI M , et al . On the catalytic mechanism and stereospecificity of Escherichia coli L-threonine aldolase [J ] . The FEBS Journal , 2014 , 281 ( 1 ): 129 - 145 .

何远志 , 冯雁 . 苏氨酸醛缩酶的结构与功能及其在药物合成中的应用 [J ] . 生物化学与生物物理进展 , 2023 , 50 ( 5 ): 962 - 977 .

HE Y Z , FENG Y . Structure and function of threonine aldolase and its application in pharmaceutical synthesis [J ] . Progress in Biochemistry and Biophysics , 2023 , 50 ( 5 ): 962 - 977 .

WANG L C , XU L , SU B M , et al . Improving the C β stereoselectivity of L-threonine aldolase for the synthesis of L- threo -4-methylsulfonylphenylserine by modulating the substrate-binding pocket to control the orientation of the substrate entrance [J ] . Chemistry , 2021 , 27 ( 37 ): 9654 - 9660 .

LI L H , ZHANG R Z , XU Y , et al . Comprehensive screening strategy coupled with structure-guided engineering of L-threonine aldolase from Pseudomonas putida for enhanced catalytic efficiency towards L- threo -4-methylsulfonylphenylserine [J ] . Frontiers in Bioengineering and Biotechnology , 2023 , 11 : 1117890 .

LIU Z C , CHEN X , CHEN Q J , et al . Engineering of L-threonine aldolase for the preparation of 4-(methylsulfonyl)phenylserine, an important intermediate for the synthesis of florfenicol and thiamphenicol [J ] . Enzyme and Microbial Technology , 2020 , 137 : 109551 .

CHEN Q J , CHEN X , FENG J H , et al . Improving and inverting C β -stereoselectivity of threonine aldolase via substrate-binding-guided mutagenesis and a stepwise visual screening [J ] . ACS Catalysis , 2019 , 9 ( 5 ): 4462 - 4469 .

ZHENG W L , PU Z J , XIAO L X , et al . Mutability-landscape-guided engineering of L-threonine aldolase revealing the prelog rule in mediating diastereoselectivity of C—C bond formation [J ] . Angewandte Chemie International Edition , 2023 , 62 ( 2 ): e202213855 .

ZHENG W L , YU H R , FANG S , et al . Directed evolution of L-threonine aldolase for the diastereoselective synthesis of β-hydroxy-α-amino acids [J ] . ACS Catalysis , 2021 , 11 ( 6 ): 3198 - 3205 .

PARK S H , SEO H , SEOK J W , et al . Cβ-selective aldol addition of D-threonine aldolase by spatial constraint of aldehyde binding [J ] . ACS Catalysis , 2021 , 11 ( 12 ): 6892 - 6899 .

ZHENG W L , CHEN K T , WANG Z , et al . Construction of a highly diastereoselective aldol reaction system with L-threonine aldolase by computer-assisted rational molecular modification and medium engineering [J ] . Organic Letters , 2020 , 22 ( 15 ): 5763 - 5767 .

FANG S , YU H R , XIAO L X , et al . Counteracting the activity-diastereoselectivity trade-off of L-threonine aldolase by regulating the proton transfer microenvironment [J ] . Advanced Synthesis & Catalysis , 2022 , 364 ( 24 ): 4363 - 4370 .

HE Y Z , LI S Y , WANG J , et al . Discovery and engineering of the L-threonine aldolase from Neptunomonas marine for the efficient synthesis of β-hydroxy-α-amino acids via C—C formation [J ] . ACS Catalysis , 2023 , 13 ( 11 ): 7210 - 7220 .

FERNANDES H S , RAMOS M J , CERQUEIRA N M F S A . Catalytic mechanism of the serine hydroxymethyltransferase: a computational ONIOM QM/MM study [J ] . ACS Catalysis , 2018 , 8 ( 11 ): 10096 - 10110 .

SANTATIWONGCHAI J , GLEESON D , GLEESON M P . Theoretical evaluation of the reaction mechanism of serine hydroxymethyltransferase [J ] . The Journal of Physical Chemistry B , 2019 , 123 ( 2 ): 407 - 418 .

HERNANDEZ K , ZELEN I , PETRILLO G , et al . Engineered L-serine hydroxymethyltransferase from Streptococcus thermophilus for the synthesis of α, α-dialkyl-α-amino acids [J ] . Angewandte Chemie International Edition , 2015 , 54 ( 10 ): 3013 - 3017 .

ANGELACCIO S , FLORIO R , CONSALVI V , et al . Serine hydroxymethyltransferase from the cold adapted microorganism Psychromonas ingrahamii : a low temperature active enzyme with broad substrate specificity [J ] . International Journal of Molecular Sciences , 2012 , 13 ( 2 ): 1314 - 1326 .

MA′RUF I F , RESTIAWATY E , SYIHAB S F , et al . Characterization of thermostable serine hydroxymethyltransferase for β-hydroxy amino acids synthesis [J ] . Amino Acids , 2023 , 55 ( 1 ): 75 - 88 .

KUMAR A , WU G B , WU Z , et al . Improved catalytic properties of a serine hydroxymethyl transferase from Idiomarina loihiensis by site directed mutagenesis [J ] . International Journal of Biological Macromolecules , 2018 , 117 : 1216 - 1223 .

ZUO Z Y , ZHENG Z L , LIU Z G , et al . Cloning, DNA shuffling and expression of serine hydroxymethyltransferase gene from Escherichia coli strain AB90054 [J ] . Enzyme and Microbial Technology , 2007 , 40 ( 4 ): 569 - 577 .

TENG Z X , PAN X W , LIU Y R , et al . Engineering serine hydroxymethyltransferases for efficient synthesis of L-serine in Escherichia coli [J ] . Bioresource Technology , 2024 , 393 : 130153 .

GWON H J , YOSHIOKA H , SONG N E , et al . Optimal production of L- threo -2,3-dihydroxyphenylserine (L- threo -DOPS) on a large scale by diastereoselectivity-enhanced variant of L-threonine aldolase expressed in Escherichia coli [J ] . Preparative Biochemistry & Biotechnology , 2012 , 42 ( 2 ): 143 - 154 .

TENG H D , CHEN K T , WANG L , et al . Rational immobilization of L-threonine aldolase from Bacillus nealsonii for efficiently synthesis of L- syn -3-[4-(methylsulfonyl) ] phenylserine [J ] . Process Biochemistry , 2023 , 130 : 685 - 694 .

CAI B Q , BOCOLA M , ZHOU A M , et al . Computer-aided directed evolution of L-threonine aldolase for asymmetric biocatalytic synthesis of a chloramphenicol intermediate [J ] . Bioorganic & Medicinal Chemistry , 2022 , 68 : 116880 .

XI Z W , LI L H , ZHANG X Y , et al . Expanding the L-threonine transaldolase toolbox for the diastereomeric synthesis of β-hydroxy-α-amino acids [J ] . Molecular Catalysis , 2023 , 543 : 113139 .

WANG L C , XU L , SU B M , et al . An effective chemo-enzymatic method with an evolved L-threonine aldolase for preparing L- threo -4-methylsulfonylphenylserine ethyl ester of high optical purity [J ] . Molecular Catalysis , 2022 , 525 : 112355 .

ZHENG W L , CHEN K T , FANG S , et al . Construction and application of PLP self-sufficient biocatalysis system for threonine aldolase [J ] . Enzyme and Microbial Technology , 2020 , 141 : 109667 .

GONG L , XIU Y S , DONG J J , et al . Sustainable one-pot chemo-enzymatic synthesis of chiral furan amino acid from biomass via magnetic solid acid and threonine aldolase [J ] . Bioresource Technology , 2021 , 337 : 125344 .

SEO Y M , MATHEW S , BEA H S , et al . Deracemization of unnatural amino acid: homoalanine using D-amino acid oxidase and ω-transaminase [J ] . Organic & Biomolecular Chemistry , 2012 , 10 ( 12 ): 2482 - 2485 .

MOLLA G , MELIS R , POLLEGIONI L . Breaking the mirror: L-amino acid deaminase, a novel stereoselective biocatalyst [J ] . Biotechnology Advances , 2017 , 35 ( 6 ): 657 - 668 .

WU L C , GUO X L , WU G B , et al . Efficient enzymatic synthesis of α-keto acids by redesigned substrate-binding pocket of the L-amino acid deaminase (PmiLAAD) [J ] . Enzyme and Microbial Technology , 2020 , 132 : 109393 .

WALTON C J W , PARMEGGIANI F , BARBER J E B , et al . Engineered aminotransferase for the production of D-phenylalanine derivatives using biocatalytic cascades [J ] . ChemCatChem , 2018 , 10 ( 2 ): 470 - 474 .

HAN S W , SHIN J S . One-pot preparation of d-amino acids through biocatalytic deracemization using alanine dehydrogenase and ω-transaminase [J ] . Catalysis Letters , 2018 , 148 ( 12 ): 3678 - 3684 .

ISHIDA C , MIYATA R , HASEBE F , et al . Reconstruction of hyper-thermostable ancestral L-amino acid oxidase to perform deracemization to D-amino acids [J ] . ChemCatChem , 2021 , 13 ( 24 ): 5228 - 5235 .

NAKANO S , KOZUKA K , MINAMINO Y , et al . Ancestral L-amino acid oxidases for deracemization and stereoinversion of amino acids [J ] . Communications Chemistry , 2020 , 3 ( 1 ): 181 .

ZHU L B , FENG G Q , GE F , et al . One-pot enzymatic synthesis of D-arylalanines using phenylalanine ammonia lyase and L-amino acid deaminase [J ] . Applied Biochemistry and Biotechnology , 2019 , 187 ( 1 ): 75 - 89 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Applications of protein engineering in pharmaceutical industry

Recent advances in photo-induced promiscuous enzymatic reactions

Research progress of artificial intelligence in desiging protein structures

Recent development of directed evolution in protein engineering

Related Author

WANG Ziyuan

YANG Lirong

WU Jianping

WEN Yanhua

LIU Hedong

CAO Chunlai

WU Ruibo

XU Weihua

Related Institution

College of Chemical and Biological Engineering， Zhejiang University

The United Biotechnology （Zhuhai Hengqin） Co.， Ltd.

Zhuhai United Laboratories Co.， Ltd

School of Pharmaceutical Science，Sun Yat-Sen University

Department of Chemistry，Zhejiang University

⁰