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[1]赵 锦,吴有斌.微生物来源青霉素酰化酶固定化载体构建研究进展 [J].武汉工程大学学报,2026,48(04):418-425.[doi:10.19843/j.cnki.CN42-1779/TQ.202605014]
 ZHAO Jin,WU Youbin. Research progress on the construction of immobilization carriers for microbe-derived penicillin G acylase [J].Journal of Wuhan Institute of Technology,2026,48(04):418-425.[doi:10.19843/j.cnki.CN42-1779/TQ.202605014]
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微生物来源青霉素酰化酶固定化载体构建研究进展
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《武汉工程大学学报》[ISSN:1674-2869/CN:42-1779/TQ]

卷:
48
期数:
2026年04期
页码:
418-425
栏目:
现代大化工
出版日期:
2026-08-30

文章信息/Info

Title:
Research progress on the construction of immobilization carriers for microbe-derived penicillin G acylase


文章编号:
1674 - 2869(2026)04 - 0418 - 08
作者:
赵 锦1吴有斌2
1. 湖北轻工职业技术学院轻化工程学院,湖北 武汉 430070;
2. 宜昌人福药业有限责任公司产品开发中心,湖北 宜昌 443000

Author(s):
ZHAO Jin1WU Youbin2
1. School of Light Chemical Engineering, Hubei Light Industry Technology Institute, Wuhan 430070, China;
2. R&D Department, Yichang Humanwell Pharmaceutical Co., Ltd., Yichang 443000, China

关键词:
青霉素酰化酶固定化载体表面修饰金属有机骨架酶学性能工业生物催化
Keywords:
penicillin G acylase (PGA) immobilization carrier surface modification metal-organic framework enzymatic performance industrial biocatalysis
分类号:
TQ465;Q55
DOI:
10.19843/j.cnki.CN42-1779/TQ.202605014
文献标志码:
A
摘要:
青霉素酰化酶(PGA)是6-氨基青霉烷酸及半合成β-内酰胺类抗生素绿色制造中的关键生物催化剂。围绕“结构特征—载体构建—固定化策略—性能评价—工业适配”的逻辑,梳理近年有机高分子、无机/磁性纳米材料、金属有机骨架(MOFs)及天然传统载体研究文献,系统综述微生物源青霉素酰化酶固定化载体的构建相关研究进展。研究表明:亲水高分子载体有利于维持酶分子表面水化层;磁性纳米载体便于快速催化剂回收;MOFs在孔道限域和微环境调控方面具有潜力;连续流和固定床评价正在成为连接材料设计与工业应用的重要方向。当前研究仍存在载体成本偏高、传质限制、酶分子取向调控和长期运行稳定性不足等问题。后续研究需聚焦低成本载体、酶定向固定化、层级孔结构和连续化反应器的协同设计,推动固定化PGA催化剂在β-内酰胺类抗生素绿色制造中的规模化应用。
Abstract:
Penicillin G acylase (PGA) acts as a key biocatalyst for the green manufacturing of 6-aminopenicillanic acid and semi-synthetic β-lactam antibiotics. In this review, we systematically summarized recent progress on PGA immobilization carriers by following a unified framework of “structural characteristics-support fabrication-immobilization strategy-performance evaluation-industrial adaptability”, covering organic polymers, inorganic/magnetic nanomaterials, metal-organic frameworks (MOFs), and traditional natural carriers. Existing studies reveal that hydrophilic polymer carriers help preserve the hydration shell of enzymes; magnetic nanocarriers facilitate rapid catalyst recovery; MOFs exhibit great potential in pore confinement and microenvironment regulation; evaluation via continuous-flow and fixed-bed systems has become a vital bridge between material design and industrial application. Several bottlenecks remain unresolved, including high carrier cost, mass transfer limitation, poor controllability of enzyme orientation, and insufficient stability during long-term operation. Future research should strengthen the collaborative design of low-cost carriers, oriented immobilization, hierarchical pore structures and continuous reactors, so as to promote large-scale application of immobilized PGA in the green production of β-lactam antibiotics.

参考文献/References:

[ 1 ] DUGGLEBY H J, TOLLEY S P, HILL C P, et al. Penicillin acylase has a single-amino-acid catalytic centre [J]. Nature, 1995, 373(6511): 264-268.
[ 2 ] LIU C L, WANG X D, CHEN Z B, et al. The immobilization of penicillin G acylase on modified TiO2 with various micro-environments [J]. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2021, 616: 126316.
[ 3 ] LI K, MOHAMMED M A A, ZHOU Y S, et al. Recent progress in the development of immobilized penicillin G acylase for chemical and industrial applications: a mini-review [J]. Polymers for Advanced Technologies, 2020, 31(3): 368-388.
[ 4 ] PAN X, XU L, LI Y R, et al. Strategies to improve the biosynthesis of β-lactam antibiotics by penicillin G acylase: progress and prospects [J]. Frontiers in Bioengineering and Biotechnology, 2022, 10: 936487.
[ 5 ] SHELDON R A, VAN PELT S. Enzyme immobilisation in biocatalysis: why, what and how [J]. Chemical Society Reviews, 2013, 42(15): 6223-6235.
[ 6 ] BASSO A, SERBAN S. Industrial applications of immobilized enzymes:a review [J]. Molecular Catalysis, 2019, 479: 110607.
[ 7 ] DA ROCHA T N, MORELLON-STERLLING R, ROCHA-MARTIN J, et al. Immobilization of penicillin G acylase on vinyl sulfone-agarose: an unexpected effect of the ionic strength on the performance of the immobilization process [J]. Molecules, 2022, 27(21): 7587.
[ 8 ] NI Y, Lü Z X, WANG Z, et al. Immobilization and evaluation of penicillin G acylase on hydroxy and aldehyde functionalized magnetic α-Fe2O3/Fe3O4 heterostructure nanosheets [J]. Frontiers in Bioengineering and Biotechnology, 2022, 9: 812403.
[ 9 ] MA M Y, CHEN X, YUE Y, et al. Immobilization and property of penicillin G acylase on amino functionalized magnetic Ni0.3Mg0.4Zn0.3Fe2O4 nanoparticles prepared via the rapid combustion process [J]. Frontiers in Bioengineering and Biotechnology, 2023, 11: 1108820.
[10] Lü Z X, WANG Z, WU S B, et al. Enhanced catalytic performance of penicillin G acylase by covalent immobilization onto functionally-modified magnetic Ni0.4Cu0.5Zn0.1Fe2O4 nanoparticles [J]. PLoS One, 2024, 19(1): e0297149.
[11] HU H, WU S C, ZHENG Y L, et al. Dynamic exchange strategy for enzyme immobilization in Zr-based metal-organic frameworks for green synthesis of β-lactam antibiotics [J]. Green Chemical Engineering, 2026, 7(4): 389-398.
[12] XUE P, GU Y H, SU W G, et al. In situ one-pot preparation of superparamagnetic hydrophilic porous microspheres for covalently immobilizing penicillin G acylase to synthesize amoxicillin [J]. Applied Surface Science, 2016, 362: 427-433.
[13] YU Q M, WANG Z, ZHANG Y W, et al. Covalent immobilization and characterization of penicillin G acylase on amino and GO functionalized magnetic Ni0.5Zn0.5Fe2O4@SiO2 nanocomposite prepared via a novel rapid-combustion process [J]. International Journal of Biological Macromolecules, 2019, 134: 507-515.
[14] WANG X D, CHEN Z J, LI K, et al. The study of titanium dioxide modification by glutaraldehyde and its application of immobilized penicillin acylase [J]. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2019, 560: 298-305.
[15] YANG L,GAO Z Y,GUO Y L, et al. Immobilization of penicillin G acylase on paramagnetic aldehyde-functionalized mesostructured cellular foams [J]. Enzyme and Microbial Technology, 2014, 60: 32-39.
[16] LING X M, WANG X Y, MA P, et al. Covalent immobilization of penicillin G acylase onto Fe3O4@Chitosan magnetic nanoparticles [J]. Journal of Microbiology and Biotechnology, 2016, 26(5): 829-836.
[17] LI X, TIAN L, ALI Z, et al. Design of flexible dendrimer-grafted flower-like magnetic microcarriers for penicillin G acylase immobilization [J]. Journal of Materials Science, 2018, 53(2): 937-947.
[18] XUE P, SU W G, GU Y H, et al. Hydrophilic porous magnetic poly(GMA-MBAA-NVP) composite microspheres containing oxirane groups: an efficient carrier for immobilizing penicillin G acylase [J]. Journal of Magnetism and Magnetic Materials, 2015, 378: 306-312.
[19] LIESE A, HILTERHAUS L. Evaluation of immobilized enzymes for industrial applications [J]. Chemical Society Reviews, 2013, 42(15): 6236.
[20] CAO L Q, VAN LANGEN L, SHELDON R A. Immobilised enzymes: carrier-bound or carrier-free? [J]. Current Opinion in Biotechnology, 2003, 14(4): 387-394.
[21] 曲红波, 丛威, 王贞, 等. 一种新型固定化青霉素酰化酶的性能及动力学常数的测定[J]. 化工冶金, 1999(1): 51-56.
[22] 薛屏, 王居兰, 李鹏. 固定化酶球形高分子载体的设计与应用[J]. 石油化工, 2010, 39(1): 7-12.
[23] DA ROCHA T N, MORELLON-STERLING R, GON?ALVES L R B, et al. Synergy of ion exchange and covalent reaction: immobilization of penicillin G acylase on heterofunctional amino-vinyl sulfone agarose [J]. Catalysts, 2023, 13(1): 151.
[24] ZHANG B Y, ZHOU Y S, LIU C L, et al. Immobilized penicillin G acylase with enhanced activity and stability using glutaraldehyde-modified polydopamine-coated Fe3O4 nanoparticles [J]. Biotechnology and Applied Biochemistry, 2022, 69(2): 629-641.
[25] LUO X G, ZHANG L N. Immobilization of penicillin G acylase in epoxy-activated magnetic cellulose microspheres for improvement of biocatalytic stability and activities [J]. Biomacromolecules, 2010, 11(11): 2896-2903.
[26] Lü Y, LU G, WANG Y, et al. Functionalization of cubic Ia3d mesoporous silica for immobilization of penicillin G acylase [J]. Advanced Functional Materials, 2007, 17(13): 2160-2166.
[27] ZHAN W C, Lü Y J, YANG L, et al. Epoxidation of vinyl functionalized cubic Ia3d mesoporous silica for immobilization of penicillin G acylase [J]. Chinese Journal of Catalysis, 2014, 35(10): 1709-1715.
[28] ZHAO J Q, WANG Y J, LUO G S, et al. Immobilization of penicillin G acylase on macro-mesoporous silica spheres [J]. Bioresource Technology, 2011, 102(2): 529-535.
[29] ?U?A M G, OBRADOVI? B M, KNE?EVI?-JUGOVI? Z D. Hydrolysis of penicillin G by penicillin G acylase immobilized on chitosan microbeads in different reactor systems [J]. Chemical Engineering & Technology, 2011, 34(10): 1706-1714.
[30] MISLOVI?OVá D, MASáROVá J, VIKARTOVSKá A, et al. Biospecific immobilization of mannan-penicillin G acylase neoglycoenzyme on Concanavalin A-bead cellulose [J]. Journal of Biotechnology, 2004, 110(1): 11-19.
[31] LI Y X, SU X Q, YE Q L. A polyacrylic acid as a carrier for immobilization of penicillin acylase [J]. Journal of Applied Polymer Science, 2002, 86(8): 2067-2069.
[32] MOHAMMED M A A, CHEN Z, LI K, ZHANG B. The study of Fe3O4@SiO2-NH2 nano-magnetic composite modified by glutaraldehyde to immobilized penicillin G acylase[J]. Turkish Journal of Chemistry, 2022, 46(1): 103-115.
[33] TU H Y, GAO K K, ZHANG B Y, et al. Comparative study of poly tannic acid functionalized magnetic particles before and after modification for immobilized penicillin G acylase [J]. Journal of Biomaterials Science, Polymer Edition, 2022, 33(7): 823-846.
[34] TU H Y, NIU F F, LI X Z, et al. Nanoarchitectonics of penicillin G acylase with Mn2+ doped β-cyclodextrin/Fe3O4 for enhanced catalytic activity and reusability [J]. Molecular Catalysis, 2023, 535: 112838.
[35] WANG X L, SHI J F, ZHANG S H, et al. MOF-templated rough, ultrathin inorganic microcapsules for enzyme immobilization [J]. Journal of Materials Chemistry B, 2015, 3(32): 6587-6598.
[36] HU Y L, DAI L M, LIU D H, et al. Progress & prospect of metal-organic frameworks (MOFs) for enzyme immobilization (enzyme/MOFs) [J]. Renewable and Sustainable Energy Reviews, 2018, 91: 793-801.
[37] WANG X L, LAN P C, MA S Q. Metal-organic frameworks for enzyme immobilization: beyond host matrix materials [J]. ACS Central Science, 2020, 6(9): 1497-1506.
[38] VALENCIA P, WILSON L, AGUIRRE C, et al. Evaluation of the incidence of diffusional restrictions on the enzymatic reactions of hydrolysis of penicillin G and synthesis of cephalexin [J]. Enzyme and Microbial Technology, 2010, 47(6): 268-276.
[39] MAGHRABY Y R, EL-SHABASY R M, IBRAHIM A H, et al. Enzyme immobilization technologies and industrial applications [J]. ACS Omega, 2023, 8(6): 5184-5196.
[40] ROGACKA J, LABUS K. Metal-organic frameworks as highly effective platforms for enzyme immobilization-current developments and future perspectives [J]. Brazilian Journal of Chemical Engineering, 2025, 42(4): 1273-1301.
[41] TANG Z Y, OKU Y, MATSUDA T. Application of immobilized enzymes in flow biocatalysis for efficient synthesis [J]. Organic Process Research & Development, 2024, 28(5): 1308-1326.
[42] FERNáNDEZ REGUEIRO C L, ROURA PADROSA D, PARADISI F. Biocatalysis in packed-bed reactors: immobilization as an enabling technology [J]. Comptes Rendus Chimie, 2025, 28(G1): 349-359.
[43] SENTHIL RAJA D, TSAI D H. Recent advances in continuous flow synthesis of metal-organic frameworks and their composites [J]. Chemical Communications, 2024, 60(65): 8497-8515.
[44] ZHANG Z Z, GAO L, BOES A, et al. An enzymatic continuous-flow reactor based on a pore-size matching nano- and isoporous block copolymer membrane [J]. Nature Communications, 2024, 15: 3308.

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备注/Memo

备注/Memo:
收稿日期:2026-05-26
基金项目:全国生物技术职业教育教学指导委员会生物技术领域职业教育教学关键要素改革培育项目(SWXMGJYS 2026045);湖北省新时代职业学校名师(名匠)名校长培养计划(鄂教职成办函[2026]2号)
作者简介:赵 锦,硕士,副教授。Email:254699465@qq.com

更新日期/Last Update: 2026-09-05