Application of multi-enzyme catalytic system in the synthesis of pharmaceutical chemicals

TANG Heng; HAN Xin; ZOU Shuping; ZHENG Yuguo

doi:10.12211/2096-8280.2021-028

您当前的位置：

首页 >

文章列表页 >

Application of multi-enzyme catalytic system in the synthesis of pharmaceutical chemicals

Invited Review | 更新时间：2026-03-05

- Application of multi-enzyme catalytic system in the synthesis of pharmaceutical chemicals
- Synthetic Biology Journal Vol. 2, Issue 4, Pages: 559-576(2021)
- 作者机构：
  
  浙江工业大学生物工程学院手性生物制造国家地方联合工程研究中心，浙江杭州 310014
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2021-028
  CLC： Q814.9
- Received：24 February 2021，
  
  Revised：2021-05-25，
  
  Published：31 August 2021
- 稿件说明：
移动端阅览
汤恒，韩鑫，邹树平，郑裕国. 多酶催化体系在医药化学品合成中的应用［J］. 合成生物学， 2021， 2（4）： 559-576

TANG Heng， HAN Xin， ZOU Shuping， ZHENG Yuguo. Application of multi-enzyme catalytic system in the synthesis of pharmaceutical chemicals［J］. Synthetic Biology Journal， 2021， 2（4）： 559-576
汤恒，韩鑫，邹树平，郑裕国. 多酶催化体系在医药化学品合成中的应用［J］. 合成生物学， 2021， 2（4）： 559-576 DOI： 10.12211/2096-8280.2021-028.

TANG Heng， HAN Xin， ZOU Shuping， ZHENG Yuguo. Application of multi-enzyme catalytic system in the synthesis of pharmaceutical chemicals［J］. Synthetic Biology Journal， 2021， 2（4）： 559-576 DOI： 10.12211/2096-8280.2021-028.

摘要

多酶催化体系成为近年来生物催化领域的研究热点。由于过程可控性及下游易分离的特性，越来越多的体外多酶催化体系已成功构建，部分体系还可耦合化学催化步骤，应用于精细化学品的合成。随着多酶催化体系构建技术的逐步成熟，将会给未来化工与医药类产品的生物制造带来广阔的应用前景。本文介绍了多酶催化体系的相关设计原则，通过对反应过程和合成路径进行热力学和动力学分析，设计高价值产物的生物合成路径，挖掘路径中的关键酶，结合各类新型组装策略将功能各异的酶级联组装成一个结构和功能整体，形成“底物通道”，减少中间体损失和降低副反应，实现从简单底物向复杂产物的高效生物转化。系统分析了多酶催化体系在医药化学品（如抗生素、抗癌药物、心血管疾病治疗药物、肝病治疗药物和精神疾病治疗药物及各类活性成分如D-葡萄糖二酸、萜类化合物和5-氨基乙酰丙酸）合成中的应用实例，并总结多酶催化体系仍存在的问题及可能的解决方法。

Abstract

The multi-enzyme catalysis system has become a hotspot in the field of bio-catalysis in recent years. Due to the catalytic process's controllability and the ease of downstream separation

more and more intracellular metabolic pathways are being developed and applied to produce fine chemicals

in vitro

. With the gradual maturity of multi-enzyme catalytic system construction technology

it will bring a broad application prospect for the manufacture of chemical products and pharmaceutical products in the future. In this regard

we review recently published examples of multi-enzyme catalysis

compare relevant design principles. Thermodynamics and kinetics of the reaction process and synthesis path analysis are used to design a bio-catalysis path. The critical enzymes are then mined in the pathway. By combining various assembly strategies

enzymes with different functions are cascaded into a whole structure and function unit to form a "substrate channel." Then intermediate loss and side reaction was reduced during the efficient bioconversion process from simple substrates to complex products. This method has the advantages of improving reaction efficiency

high regional selectivity and stereoselectivity

and also reducing environmental impact. Thus

biocatalysts are now widely used to produce valuable commercial chemicals

pharmaceuticals

and fuels. The target products could be obtained by the bio-catalysis process

in vivo

in vitro

. High-value products that are difficult to synthesize

or in an extremely complex synthesis pathway

or a very costly synthesis process by non-biological methods can now be produced in microbial hosts. To match the corresponding products

various genes in the host cell need to be optimized and fine-tuned. However

in vitro

bio-catalysis can avoid these limitations. By adding a variety of enzymes to the reaction system

the product can be obtained after completing the catalysis at one time. Thus

industrial bio-fabrication has emerged as an attractive and economically viable alternative to conventional large-scale chemical synthesis. The multi-enzyme catalysis system in the synthesis of pharmaceutical chemicals (such as antibiotics

drugs for anti-cancer

cardiovascular disease treatment

liver disease treatment and psychiatric treatment) and various active ingredients (such as D-gluconic acid

terpenoids

5-aminolevulinic acid) were discussed. The problems existing in the multi-enzyme catalytic system and the possible solutions are also summarized.

关键词

Keywords

references

CASTELLANA M , WILSON M Z , XU Y , et al . Enzyme clustering accelerates processing of intermediates through metabolic channeling [J ] . Nature Biotechnology , 2014 , 32 ( 10 ): 1011 - 1018 .

WARNECKE T , GILL R T . Organic acid toxicity, tolerance, and production in Escherichia coli biorefining applications [J ] . Microbial Cell Factories , 2005 , 4 : 25 .

GRAHAM J W A , WILLIAMS T C R , MORGAN M , et al . Glycolytic enzymes associate dynamically with mitochondria in response to respiratory demand and support substrate channeling [J ] . The Plant Cell , 2007 , 19 ( 11 ): 3723 - 3738 .

HAGGIE P M , VERKMAN A S . Diffusion of tricarboxylic acid cycle enzymes in the mitochondrial matrix in vivo . Evidence for restricted mobility of a multienzyme complex [J ] . The Journal of Biological Chemistry , 2002 , 277 ( 43 ): 40782 - 40788 .

DING S Y , HIMMEL M E . The maize primary cell wall microfibril: a new model derived from direct visualization [J ] . Journal of Agricultural and Food Chemistry , 2006 , 54 ( 3 ): 597 - 606 .

GECK M K , KIRSCH J F . A novel, definitive test for substrate channeling illustrated with the aspartate aminotransferase/malate dehydrogenase system [J ] . Biochemistry , 1999 , 38 ( 25 ): 8032 - 8037 .

ZHANG Y H . Substrate channeling and enzyme complexes for biotechnological applications [J ] . Biotechnology Advances , 2011 , 29 ( 6 ): 715 - 725 .

WOODLEY J M . Microbial biocatalytic processes and their development [J ] . Advances in Applied Microbiology , 2006 , 60 : 1 - 15 .

许可 , 吕波 , 李春 . 无细胞的合成生物技术——多酶催化与生物合成 [J ] . 中国科学:化学 , 2015 , 45 ( 5 ): 429 - 437 .

XU K , LÜ B , LI C . Cell-free synthetic biotechnology — multi-enzyme catalysis and biosynthesis [J ] . Scientia Sinica Chimica , 2015 , 45 ( 5 ): 429 - 437 .

SCHOFFELEN S , VAN HEST J C M . Multi-enzyme systems: bringing enzymes together in vitro [J ] . Soft Matter , 2012 , 8 ( 6 ): 1736 - 1746 .

FEIST A M , PALSSON B Ø . The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli [J ] . Nature Biotechnology , 2008 , 26 ( 6 ): 659 - 667 .

HAWKINS K M , SMOLKE C D . Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae [J ] . Nature Chemical Biology , 2008 , 4 ( 9 ): 564 - 573 .

FRANCE S P , HEPWORTH L J , TURNER N J , et al . Constructing biocatalytic cascades: in vitro and in vivo approaches to de novo multi-enzyme pathways [J ] . ACS Catalysis , 2016 , 7 ( 1 ): 710 - 724 .

BACHMANN B O . Biosynthesis: Is it time to go retro? [J ] . Nature Chemical Biology , 2010 , 6 ( 6 ): 390 - 393 .

DELÉPINE B , DUIGOU T , CARBONELL P , et al . RetroPath2.0: A retrosynthesis workflow for metabolic engineers [J ] . Metabolic Engineering , 2018 , 45 : 158 - 170 .

KUMAR A , WANG L , NG C Y , et al . Pathway design using de novo steps through uncharted biochemical spaces [J ] . Nature Communications , 2018 , 9 ( 1 ): 184 .

SHI J F , WU Y Z , ZHANG S H , et al . Bioinspired construction of multi-enzyme catalytic systems [J ] . Chemical Society Reviews , 2018 , 47 ( 12 ): 4295 - 4313 .

MUTTI F G , KNAUS T , SCRUTTON N S , et al . Conversion of alcohols to enantiopure amines through dual-enzyme hydrogen-borrowing cascades [J ] . Science , 2015 , 349 ( 6255 ): 1525 - 1529 .

KIM Y H , CAMPBELL E , YU J , et al . Complete oxidation of methanol in biobattery devices using a hydrogel created from three modified dehydrogenases [J ] . Angewandte Chemie (International Ed in English) , 2013 , 52 ( 5 ): 1437 - 1440 .

ANDRE C , KIM S W , YU X H , et al . Fusing catalase to an alkane-producing enzyme maintains enzymatic activity by converting the inhibitory byproduct H 2 O 2 to the cosubstrate O 2 [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2013 , 110 ( 8 ): 3191 - 3196 .

QUIN M B , WALLIN K K , ZHANG G , et al . Spatial organization of multi-enzyme biocatalytic cascades [J ] . Organic & Biomolecular Chemistry , 2017 , 15 ( 20 ): 4260 - 4271 .

ZHANG G Q , QUIN M B , SCHMIDT-DANNERT C . Self-assembling protein scaffold system for easy in vitro coimmobilization of biocatalytic cascade enzymes [J ] . ACS Catalysis , 2018 , 8 ( 6 ): 5611 - 5620 .

DELEBECQUE C J , LINDNER A B , SILVER P A , et al . Organization of intracellular reactions with rationally designed RNA assemblies [J ] . Science , 2011 , 333 ( 6041 ): 470 - 474 .

MYHRVOLD C , POLKA J K , SILVER P A . Synthetic lipid-containing scaffolds enhance production by colocalizing enzymes [J ] . ACS Synthetic Biology , 2016 , 5 ( 12 ): 1396 - 1403 .

POLKA J K , HAYS S G , SILVER P A . Building spatial synthetic biology with compartments, scaffolds, and communities [J ] . Cold Spring Harbor Perspectives in Biology , 2016 , 8 ( 8 ): a024018 .

AGAPAKIS C M , BOYLE P M , SILVER P A . Natural strategies for the spatial optimization of metabolism in synthetic biology [J ] . Nature Chemical Biology , 2012 , 8 ( 6 ): 527 - 535 .

GIESSEN T W , SILVER P A . Encapsulation as a strategy for the design of biological compartmentalization [J ] . Journal of Molecular Biology , 2016 , 428(5pt b): 916- 927 .

LEE H , DELOACHE W C , DUEBER J E . Spatial organization of enzymes for metabolic engineering [J ] . Metabolic Engineering , 2012 , 14 ( 3 ): 242 - 251 .

YEATES T O , CROWLEY C S , TANAKA S . Bacterial microcompartment organelles: protein shell structure and evolution [J ] . Annual Review of Biophysics , 2010 , 39 : 185 - 205 .

BOBIK T A , LEHMAN B P , YEATES T O . Bacterial microcompartments: widespread prokaryotic organelles for isolation and optimization of metabolic pathways [J ] . Molecular Microbiology , 2015 , 98 ( 2 ): 193 - 207 .

LAWRENCE A D , FRANK S , NEWNHAM S , et al . Solution structure of a bacterial microcompartment targeting peptide and its application in the construction of an ethanol bioreactor [J ] . ACS Synthetic Biology , 2014 , 3 ( 7 ): 454 - 465 .

LI C , ZHANG R , WANG J , et al . Protein engineering for improving and diversifying natural product biosynthesis [J ] . Trends in Biotechnology , 2020 , 38 ( 7 ): 729 - 744 .

XUE R , WOODLEY J M . Process technology for multi-enzymatic reaction systems [J ] . Bioresource Technology , 2012 , 115 : 183 - 195 .

WAHL C , HIRTZ D , ELLING L . Multiplexed capillary electrophoresis as analytical tool for fast optimization of multi-enzyme cascade reactions - synthesis of nucleotide sugars: Dedicated to Prof. Dr. Vladimir Křen on the occasion of his 60 th birthday [J ] . Biotechnology Journal , 2016 , 11 ( 10 ): 1298 - 1308 .

ARANAZ I , ACOSTA N , FéRNANDEZ-VALLE M E , et al . Optimization of D-amino acid production catalyzed by immobilized multi-enzyme system in polyelectrolyte complex gel capsules [J ] . Journal of Molecular Catalysis B: Enzymatic , 2015 , 121 : 45 - 52 .

KIM Y , YOON K , KHANG Y , et al . The 2.0 Å crystal structure of cephalosporin acylase [J ] . Structure , 2000 , 8 ( 10 ): 1059 - 1068 .

HAMAD B . The antibiotics market [J ] . Nature Reviews Drug Discovery , 2010 , 9 ( 9 ): 675 - 676 .

DING J M , ZHOU Y , ZHU H J , et al . Characterization of EstZY: a new acetylesterase with 7-aminocephalosporanic acid deacetylase activity from Alicyclobacillus tengchongensis [J ] . International Journal of Biological Macromolecules , 2020 , 148 : 333 - 341 .

TAKIMOTO A , TAKAKURA T , TANI H , et al . Batch production of deacetyl 7-aminocephalosporanic acid by immobilized cephalosporin-C deacetylase [J ] . Applied Microbiology and Biotechnology , 2004 , 65 ( 3 ): 263 - 267 .

YAMANAKA H , CHIBA T , KAWABATA K , et al . Studies on β -lactam antibiotics IX. Synthesis and biological activity of a new orally active cephalosporin, cefixime (FK027) [J ] . The Journal of Antibiotics , 1985 , 38 ( 12 ): 1738 - 1751 .

GONZÁLEZ M , RODRÍGUEZ Z , TOLÓN B , et al . An alternative procedure for preparation of cefdinir [J ] . Farmaco , 2003 , 58 ( 6 ): 409 - 418 .

MA X Q , DENG S W , SU E Z , et al . One-pot enzymatic production of deacetyl-7-aminocephalosporanic acid from cephalosporin C via immobilized cephalosporin C acylase and deacetylase [J ] . Biochemical Engineering Journal , 2015 , 95 : 1 - 8 .

JIANG J J , CHEN X , ZHANG D L , et al . Characterization of ( R )-selective amine transaminases identified by in silico motif sequence blast [J ] . Applied Microbiology and Biotechnology , 2015 , 99 ( 6 ): 2613 - 2621 .

LEY S V , PRIOUR A . Total synthesis of the cyclic peptide Argyrin B [J ] . European Journal of Organic Chemistry , 2002 ( 23 ): 3995 - 4004 .

SHAGINIAN A , ROSEN M C , BINKOWSKI B F , et al . Solid-phase synthesis of dihydrovirginiamycin S1, a streptogramin B antibiotic [J ] . Chemistry , 2004 , 10 ( 17 ): 4334 - 4340 .

DEATON D N , GRAHAM K P , GROSS J W , et al . Thiol-based angiotensin-converting enzyme 2 inhibitors: P1' modifications for the exploration of the S1' subsite [J ] . Bioorganic & Medicinal Chemistry Letters , 2008 , 18 ( 5 ): 1681 - 1687 .

AUBELE D L , HOM R K , ADLER M , et al . Selective and brain-permeable polo-like kinase-2 (Plk-2) inhibitors that reduce α -synuclein phosphorylation in rat brain [J ] . ChemMedChem , 2013 , 8 ( 8 ): 1295 - 1313 .

SCHAROW A , KNAPPE D , REINDL W , et al . Development of bifunctional inhibitors of polo-like Kinase 1 with low-nanomolar activities against the polo-box domain [J ] . ChemBioChem , 2016 , 17 ( 8 ): 759 - 767 .

BEHRENDS M , WAGNER S , KOPKA K , et al . New matrix metalloproteinase inhibitors based on γ -fluorinated α -aminocarboxylic and α -aminohydroxamic acids [J ] . Bioorganic & Medicinal Chemistry , 2015 , 23 ( 13 ): 3809 - 3818 .

CHEN X , CUI Y F , CHENG X K , et al . Highly atom economic synthesis of d -2-aminobutyric acid through an in vitro tri-enzymatic catalytic sys tem [J ] . ChemistryOpen , 2017 , 6 ( 4 ): 534 - 540 .

SHINDE P , BANERJEE P , MANDHARE A . Marine natural products as source of new drugs: a patent review (2015—2018) [J ] . Expert Opinion on Therapeutic Patents , 2019 , 29 ( 4 ): 283 - 309 .

LIU J , HU K F , QU J P , et al . Organopromoted selectivity-switchable synthesis of polyketones [J ] . Organic Letters , 2017 , 19 ( 20 ): 5593 - 5596 .

BEN BRAÏEK O , SMAOUI S , SMAOUI S . Enterococci: between emerging pathogens and potential probiotics [J ] . BioMed Research International , 2019 , 2019 : 5938210 .

CHENG Q , XIANG L K , IZUMIKAWA M , et al . Enzymatic total synthesis of enterocin polyketides [J ] . Nature Chemical Biology , 2007 , 3 ( 9 ): 557 - 558 .

LEE G E , JOSHI B V , CHEN W , et al . Synthesis and structure-activity relationship studies of tyrosine-based antagonists at the human P2X7 receptor [J ] . Bioorganic & Medicinal Chemistry Letters , 2008 , 18 ( 2 ): 571 - 575 .

CHEN P W , LEE N C , CHIEN Y H , et al . Dia gnosis of aromatic L-amino acid decarboxylase deficiency by measuring 3- O -methyldopa concentrations in dried blood spots [J ] . Clinica Chimica Acta , International Journal of Clinical Chemistry, 2014 , 431 : 19 - 22 .

DONG W F , LIU W , LIAO X W , et al . Asymmetric total synthesis of (-)-saframycin A from L-tyrosine [J ] . The Journal of Organic Chemistry , 2011 , 76 ( 13 ): 5363 - 5368 .

OHTAKE K , YAMAGUCHI A , MUKAI T , et al . Protein stabilization utilizing a redefined codon [J ] . Scientific Reports , 2015 , 5 : 9762 .

MCCUBBIN J A , MADDESS M L , LAUTENS M . Total synthesis of cryptophycin analogues via a scaffold approach [J ] . Organic Letters , 2006 , 8 ( 14 ): 2993 - 2996 .

CHEN X C , ZHU J . Total synthesis of the marine natural product (-)‐Cribrostatin 4 (Renieramycin H) [J ] . Angewandte Chemie International Edition , 2007 , 46 ( 21 ): 3962 - 3965 .

SEYEDSAYAMDOST M R , REECE S Y , NOCERA D G , et al . Mono-, di-, tri-, and tetra-substituted fluorotyrosines: new probes for enzymes that use tyrosyl radicals in catalysis [J ] . Journal of the American Chemical Society , 2006 , 128 ( 5 ): 1569 - 1579 .

NATARAJAN A , SCHWANS J P , HERSCHLAG D . Using unnatural amino acids to probe the energetics of oxyanion hole hydrogen bonds in the ketosteroid isomerase active site [J ] . Journal of the American Chemical Society , 2014 , 136 ( 21 ): 7643 - 7654 .

LI F H , SHI P , LI J S , et al . A genetically encoded 19 F NMR probe for tyrosine phosphorylation [J ] . Angewandte Chemie (International Ed in English) , 2013 , 52 ( 14 ): 3958 - 3962 .

DI STEFANO A , SOZIO P , CERASA L S . Antiparkinson prodrugs [J ] . Molecules , 2008 , 13 ( 1 ): 46 - 68 .

SWOBODA K J , SAUL J P , MCKENNA C E , et al . Aromatic L‐amino acid decarboxylase deficiency: overview of clinical features and outcomes [J ] . Annals of Neurology , 2003 , 54 ( S6 ): S49 - S55 .

DENNIG A , BUSTO E , KROUTIL W , et al . Biocatalytic one-pot synthesis of L-tyrosine derivatives from monosubstituted benzenes, pyruvate, and ammonia [J ] . ACS Catalysis , 2015 , 5 ( 12 ): 7503 - 7506 .

DAMARAJU V L , DAMARAJU S , YOUNG J D , et al . Nucleoside anticancer drugs: the role of nucleoside transporters in resistance to cancer chemotherapy [J ] . Oncogene , 2003 , 22 ( 47 ): 7524 - 7536 .

ROBAK T , LECH-MARANDA E , KORYCKA A , et al . Purine nucleoside analogs as immunosuppressive and antineoplastic agents: mechanism of action and clinical activity [J ] . Current Medicinal Chemistry , 2006 , 13 ( 26 ): 3165 - 3189 .

MESAROS C , ARORA J S , WHOLER A , et al . 8-Oxo-2'-deoxyguanosine as a biomarker of tobacco-smoking-induced oxidative stress [J ] . Free Radical Biology & Medicine , 2012 , 53 ( 3 ): 610 - 617 .

LI Y Y , DING Q B , OU L , et al . One-pot process of 2'-deoxyguanylic acid catalyzed by a multi-enzyme system [J ] . Biotechnology and Bioprocess Engineering , 2015 , 20 ( 1 ): 37 - 43 .

ENDO A . The origin of the statins [J ] . International Congress Series , 2004 , 1262 : 3 - 8 .

PATEL R N . Biocatalysis for synthesis of pharmaceuticals [J ] . Bioorganic & Medicinal Chemistry , 2018 , 26 ( 7 ): 1252 - 1274 .

SIERRA S , RAMOS M C , MOLINA P , et al . Statins as neuroprotectants: a comparative in vitro study of lipophilicity, blood-brain-barrier penetration, lowering of brain cholesterol, and decrease of neuron cell death [J ] . Journal of Alzheimer's Disease , 2011 , 23 ( 2 ): 307 - 318 .

HOYOS P , PACE V , ALCÁNTARA A R . Biocatalyzed synthesis of statins: a sustainable strategy for the preparation of valuable drugs [J ] . Catalysts , 2019 , 9 ( 3 ): 260 .

ŠVARC A , FEKETE M , HERNANDEZ K , et al . An innovative route for the production of atorvastatin side-chain precursor by DERA-catalysed double aldol addition [J ] . Chemical Engineering Science , 2021 , 231 : 116312 .

LINDOR K D , KOWDLEY K V , HEATHCOTE E J , et al . Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial [J ] . Hepatology , 2004 , 39 ( 3 ): 770 - 778 .

ZHANG Y J , ZHENG X J , HUANG F J , et al . Ursodeoxycholic acid alters bile acid and fatty acid profiles in a mouse model of diet-induced obesity [J ] . Frontiers in Pharmacology , 2019 , 10 : 842 .

HANAFI N I , MOHAMED A S , SHEIKH A K S H , et al . Overview of bile acids signaling and perspective on the signal of ursodeoxycholic acid, the most hydrophilic bile acid, in the heart [J ] . Biomolecules , 2018 , 8 ( 4 ): 159 .

HIRSCHFIELD G M , MASON A , LUKETIC V , et al . Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid [J ] . Gastroenterology , 2015 , 148 ( 4 ): 751 - 61.e8 .

HE H W , MENNONE A , BOYER J L , et al . Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct-ligated rats and human hepatic cells [J ] . Hepatology , 2011 , 53 ( 2 ): 548 - 557 .

TONIN F , ARENDS I W . Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review [J ] . Beilstein Journal of Organic Chemistry , 2018 , 14 ( 1 ): 470 - 483 .

POLYKETIDES N T S O E , MONTI D , FERRANDI E E , et al . One-Pot multienzymatic synthesis of 12-ketoursodeoxycholic acid: subtle cofactor specificities rule the reaction equilibria of five biocatalysts working in a row [J ] . Advanced Synthesis & Catalysis , 2009 , 351 ( 9 ): 1303 - 1311 .

PANDEY R K , FERNANDES R A , KUMAR P . An asymmetric dihydroxylation route to enantiomerically pure norfluoxetine and fluoxetine [J ] . Tetrahedron Letters , 2002 , 43 ( 25 ): 4425 - 4426 .

KUMAR P , UPADHYAY R K , PANDEY R K . Asymmetric dihydroxylation route to ( R )-isoprenaline,( R )-norfluoxetine and ( R )-fluoxetine [J ] . Tetrahedron: Asymmetry , 2004 , 15 ( 24 ): 3955 - 3959 .

CAO L , LEE J , CHEN W , et al . Enantioconvergent production of ( R )-1-phenyl-1,2-ethanediol from styrene oxide by combining the Solanum tuberosum and an evolved Agrobacterium radiobacter AD1 epoxide hydrolases [J ] . Biotechnology and Bioengineering , 2006 , 94 ( 3 ): 522 - 529 .

HU Q S , XU Y , NIE Y . Highly enantioselective reduction of 2-hydroxy-1-phenylethanone to enantiopure ( R )-phenyl-1,2-ethanediol using Saccharomyces cerevisiae of remarkable reaction stability [J ] . Bioresource Technology , 2010 , 101 ( 22 ): 8502 - 8508 .

LI B , NIE Y , MU X Q , et al . De novo construction of multi-enzyme system for one-pot deracemization of ( R , S )-1-phenyl-1,2-ethanediol by stereoinversion of ( S )-enantiomer to the corresponding counterpart [J ] . Journal of Molecular Catalysis B: Enzymatic , 2016 , 129 : 21 - 28 .

RAMACHANDRAN S , FONTANILLE P , PANDEY A , et al . Gluconic acid: properties, applications and microbial production [J ] . Food Technology & Biotechnology , 2006 , 44 ( 2 ): 185 - 195 .

ANASTASSIADIS S , MORGUNOV I G . Gluconic acid production [J ] . Recent Patents on Biotechnology , 2007 , 1 ( 2 ): 167 - 180 .

SU H H , GUO Z W , WU X L , et al . Efficient bioconversion of sucrose to high-value-added glucaric acid by in vitro metabolic engineering [J ] . ChemSusChem , 2019 , 12 ( 10 ): 2278 - 2285 .

ZHAO F H , LI H , JIANG Y J , et al . Co-immobilization of multi-enzyme on control-reduced graphene oxide by non-covalent bonds: an artificial biocatalytic system for the one-pot production of gluconic acid from starch [J ] . Green Chemistry , 2014 , 16 ( 5 ): 2558 - 2565 .

PETROLL K , CARE A , BERGQUIST P L , et al . A novel framework for the cell-free enzymatic production of glucaric acid [J ] . Metabolic Engineering , 2020 , 57 : 162 - 173 .

PETROLL K , KOPP D , CARE A , et al . Tools and strategies for constructing cell-free enzyme pathways [J ] . Biotechnology Advances , 2019 , 37 ( 1 ): 91 - 108 .

OLDFIELD E , LIN F Y . Terpene biosynthesis: modularity rules [J ] . Angewandte Chemie International Edition , 2012 , 51 ( 5 ): 1124 - 1137 .

DIXON R A . Plant natural products: the molecular genetic basis of biosynthetic diversity [J ] . Current Opinion in Biotechnology , 1999 , 10 ( 2 ): 192 - 197 .

WITHERS S T , KEASLING J D . Biosynthesis and engineering of isoprenoid small molecules [J ] . Applied Microbiology and Biotechnology , 2007 , 73 ( 5 ): 980 - 990 .

KRINGS U , BERGER R G . Biotechnological production of flavours and fragrances [J ] . Applied Microbiology and Biotechnology , 1998 , 49 ( 1 ): 1 - 8 .

AJIKUMAR P K , TYO K , CARLSEN S , et al . Terpenoids: opportunities for biosynthesis of natural product drugs using engineered microorganisms [J ] . Molecular Pharmaceutics , 2008 , 5 ( 2 ): 167 - 190 .

ALONSO-GUTIERREZ J , CHAN R , BATTH T S , et al . Metabolic engineering of Escherichia coli for limonene and perillyl alcohol production [J ] . Metabolic Engineering , 2013 , 19 : 33 - 41 .

YANG J M , NIE Q J , REN M , et al . Metabolic engineering of Escherichia coli for the biosynthesis of α -pinene [J ] . Biotechnology for Biofuels , 2013 , 6 ( 1 ): 60 .

ZHANG H , LIU Q , CAO Y , et al . Microbial production of sabinene—a new terpene-based precursor of advanced biofuel [J ] . Microbial Cell Factories , 2014 , 13 : 20 .

KORMAN T P , OPGENORTH P H , BOWIE J U . A synthetic biochemistry platform for cell free production of monoterpenes from glucose [J ] . Nature Communications , 2017 , 8 : 15526 .

YANG M-L , KUN Y , GUO Y-P , et al . A photosensi tivity insecticide, 5-aminolevulinic acid, exerts effectivetoxicity to Oxya chinensis (Orthoptera: Acridoidea) [J ] . Agricultural Sciences in China , 2011 , 10 ( 7 ): 1056 - 1063 .

ZHANG J L , KANG Z , CHEN J , et al . Optimization of the heme biosynthesis pathway for the production of 5-aminolevulinic acid in Escherichia coli [J ] . Scientific Reports , 2015 , 5 : 8584 .

SASAKI K , WATANABE M , TANAKA T , et al . Biosynthesis, biotechnological production and applications of 5-aminolevulinic acid [J ] . Applied Microbiology and Biotechnology , 2002 , 58 ( 1 ): 23 - 29 .

LI T , GUO Y Y , QIAO G Q , et al . Microbial synthesis of 5-aminolevulinic acid and its coproduction with polyhydroxybutyrate [J ] . ACS Synthetic Biology , 2016 , 5 ( 11 ): 1264 - 1274 .

MENG Q L , ZHANG Y F , JU X Z , et al . Production of 5-aminolevulinic acid by cell free multi-enzyme catalysis [J ] . Journal of Biotechnology , 2016 , 226 : 8 - 13 .

WANG S Z , ZHANG Y H , REN H , et al . Strategies and perspectives of assembling multi-enzyme systems [J ] . Critical Reviews in Biotechnology , 2017 , 37 ( 8 ): 1024 - 1037 .

QIU L , CUI P F , ZHU Z L , et al . Multienzyme detection and in-situ monitoring of enzyme activity by bending CE using quantum dots-based polypeptide substrate [J ] . Electrophoresis . 2020 , 41 ( 12 ): 1103 - 1108 .

XIANG Y , ZHANG Y Y , JIANG B Y , et al . Multi-enzyme layer-by-layer assembly for dual amplified ultrasensitive electronic detection of cancer biomarkers [J ] . Sensors and Actuators B: Chemical , 2011 , 155 ( 1 ): 317 - 322 .

LIM S , KIM J , KIM Y , et al . CRISPR/Cas-directed programmable assembly of multi-enzyme complexes [J ] . Chemical Communications , 2020 , 56 ( 36 ): 4950 - 4953 .

DUDLEY Q M , KARIM A S , JEWETT M C . Cell-free metabolic engineering: biomanufacturing beyond the cell [J ] . Biotechnology Journal , 2015 , 10 ( 1 ): 69 - 82 .

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

BioHPP^®: a benchmark of biomanufacturing for high optically pure L-phosphinothricin

Chemoenzymatic synthesis of natural products: evolution of synthetic methodology and strategy

Recent development of directed evolution in protein engineering

Related Author

Yuguo ZHENG

Shuping ZOU

Xin HAN

Heng TANG

WEN Yanhua

LIU Hedong

CAO Chunlai

WU Ruibo

Related Institution

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

Zhuhai United Laboratories Co.， Ltd

School of Pharmaceutical Science，Sun Yat-Sen University

The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals， Zhejiang University of Technology

Key Laboratory of Bioorganic Synthesis of Zhejiang Province， College of Biotechnology and Bioengineering， Zhejiang University of Technology

⁰