[1]李楷原,刘 翠,邓雅姗,等.酶促制备丝裂霉素类似物反应动力学模型研究[J].江西师范大学学报(自然科学版),2022,(03):240-246.[doi:10.16357/j.cnki.issn1000-5862.2022.03.04]
 LI Kaiyuan,LIU Cui,DENG Yashan,et al.The Kinetic Modeling of the Enzymatic Preparation of Mitomycin Analogs[J].Journal of Jiangxi Normal University:Natural Science Edition,2022,(03):240-246.[doi:10.16357/j.cnki.issn1000-5862.2022.03.04]
点击复制

酶促制备丝裂霉素类似物反应动力学模型研究()
分享到:

《江西师范大学学报》(自然科学版)[ISSN:1006-6977/CN:61-1281/TN]

卷:
期数:
2022年03期
页码:
240-246
栏目:
生命与环境科学
出版日期:
2022-05-25

文章信息/Info

Title:
The Kinetic Modeling of the Enzymatic Preparation of Mitomycin Analogs
文章编号:
1000-5862(2022)03-0240-07
作者:
李楷原刘 翠邓雅姗薛 晓许 慧王繁业*
青岛科技大学化工学院制药工程系,山东 青岛 266042
Author(s):
LI KaiyuanLIU CuiDENG YashanXUE XiaoXU HuiWANG Fanye*
Department of Pharmaceutics,College of Chemical Engineering,Qingdao University of Science and Technology,Qingdao Shandong 266042,China
关键词:
固定化脂肪酶 动力学模型 Michael加成 随机双双机制 扩散限制
Keywords:
immobilized lipase kinetic modeling Michael addition random bi-bi mechanism diffusion limitation
分类号:
TQ 028.8
DOI:
10.16357/j.cnki.issn1000-5862.2022.03.04
文献标志码:
A
摘要:
基于固定化T. laibacchii脂肪酶催化2-甲基-1,4-苯醌与正丁胺的Michael加成反应建立了酶促制备丝裂霉素类似物2-甲基-3-正丁胺酰-1-氢-4-醌的反应动力学模型.该反应在柠檬酸缓冲溶液(pH值为7.0)中进行,最终产率可达98%.该文提出了修正的有序双双和随机双双机理,采用King-Altman方法得到相关微分方程组以表示即时反应速率.通过联合解微分方程和最优化方法确定动力学模型参数,使用ode45程序解微分方程组,并运用Fmincon软件计算动力学常数.研究结果表明:模型拟合值与实验值的平均相对偏差为11.25%,且偏差服从关于y=0的轴对称分布.当固定化酶粒径为0.5 mm、搅拌转速为200 rpm时可以忽略内外扩散限制.该文建立的动力学模型为固定化酶固有动力学模型.
Abstract:
The reaction kinetic model for enzymatic preparation of mitomycin analogue 2-methyl-3-n-butylamino-1-hydro-4-quinone is established based on the Michael addition reaction of 2-methyl-1,4-benzoquinone and n-butylamine catalyzed by immobilized T. laibacchii lipase.The reaction is carried out in a citric acid buffer solution(pH=7.0),and the final yield reaches 98%.In this paper,the modified ordered bi-bi and random bi-bi mechanisms are proposed,and the relevant differential equations are obtained by the King-Altman method to express the instantaneous reaction rate.The kinetic model parameters are determined by the combined solution of differential equations and optimization methods,and ode45 is used to solve the differential equations and Fmincon is used to calculate the kinetic constants.The results show that the average relative deviation between the model fitted value and the experimental value is 11.25%,and the distribution is symmetrical with zero axis.When the particle size of the immobilized enzyme is 0.5 mm and the stirring speed is 200 rpm,the experimental results show that the internal and external diffusion limitations can be ignored.Therefore,it can be seen from the above that the established kinetic model is the inherent kinetic model of the immobilized enzyme.

参考文献/References:

[1] ZHAO Min,WANG Dandan,CHE Yuan,et al.Ginsenosides synergize with mitomycin C in combating human non-small cell lung cancer by repressing Rad51-mediated DNA repair[J].Acta Pharmacologica Sinica,2018,39:449-458.
[2] NITHIANANDAM V S,ERHAN S.Quinone-amine polymers:18:a novel method for the synthesis of poly(alkyl aminoquinone)s[J].Polymer,1998,39(17):4095-4098.
[3] JEFFREY M S,SAMUEL J D.Total synthesis of gypsetin-FR-900482[J].American Chemical Society,1995,117:4722-4723.
[4] PATEL V,GAJERA H,GUPTA A,et al.Synthesis of ethyl caprylate in organic media using Candida rugosa lipase immobilized on exfoliated graphene oxide:process parameters and reusability studies[J].Biochemical Engineering Journal,2015,95:62-70.
[5] BUSTO E,GOTOR-FERNÁNDEZ V,GOTOR V.Hydrolases:catalytically promiscuous enzymes for non-conventional reactions in organic synthesis[J].Chemical Society Reviews,2010,39(11):4504-4523.
[6] YAW C T S,MOI Y C,ENG-TONG P,et al.Kinetic study of lipase-catalyzed glycerolysis of palm olein using Lipozyme TLIM in solvent-free system[J].PLOS ONE,2018,13(2):e0192375.
[7] ZHANG Yuanyuan,LIU Junhong.Kinetic study of enantioselective hydrolysis of(R,S)-ketoprofen ethyl ester using immobilized T. laibacchii lipase[J].Biochemical Engineering Journal,2011,54(1):40-46.
[8] ZHANG Yuanyuan,GAO Xin,WANG Caiyun,et al One-pot stereoselective synthesis of chiral 1,3-oxathiolane by Trichosporon laibachii lipase:Optimization by response surface methodology integrated a desirability function approach[J].Journal of Molecular Catalysis B:Enzymatic,2016,133:27-34.
[9] ZHANG Yuanyuan,LU Peiyu,SUN Qinghua,et al.Lipase-mediated direct in situ ring-opening polymerization of ε-caprolactone formed by a chemo-enzymatic method[J].Journal of Biotechnology,2018,281:74-80.
[10] 刘珊珊,刘鹏,周玲妹,等.有机相中脂肪酶的催化反应及其应用[J].发酵科技通讯,2015,44(2):52-56.
[11] 马骁,侯彬彬,赵玮钦.改性硅藻土固定化脂肪酶催化蓖麻油制备生物柴油[J].山东化工,2015,44(24):4-6,10.
[12] SHUAI Weitao,Das R K,Naghdi M,et al.A review on the important aspects of lipase immobilization on nanomaterials[J].Biotechnology and Applied Biochemistry,2017,64(4):496-508.
[13] SHELDON R A,WOODLEY J M.Role of biocatalysis in sustainable chemistry[J].Chemical Reviews,2018,118(2):801-838.
[14] 杨学昊,张增伟.交联剂固定化假丝酵母脂肪酶及其催化反应研究[J].中国油脂,2014,39(2):45-47.
[15] BAKR H E G M M.Diatomite:its characterization,modifications and applications[J].Asian Journal of Materials Science,2010,2(3):121-136.
[16] HERNANDEZ K,FERNANDEZ-LAFYUENTE R.Lipase B from Candida antarctica immobilized on octadecyl Sepabeads:a very stable biocatalyst in the presence of hydrogen peroxide[J].Process Biochemistry,2011,46(4):873-878.
[17] ZHANG Yuanyuan,LIU Junhong.Purification and in situ immobilization of lipase from of a mutant of Trichosporon laibacchii using aqueous two-phase systems[J].Journal of Chromatography B,2010,878(11):909-912.
[18] LIU Junhong,ZHANG Yuanyuan.Optimisation of lipase production by a mutant of Candida antarctica DSM-3855 using response surface methodology[J].International Journal of Food Science and Technology,2011,46(4):695-701.
[19] MARIA S,PETER C,CECILIA B,et al.Direct epoxidation in Candida antarctica lipase B studied by experiment and theory[J].ChemBioChem,2010,9(15):2443-2451.
[20] BADGUJAR,KIRTIKUMAR C,et al.Kinetic modeling and docking study of immobilized lipase catalyzed synthesis of furfuryl acetate[J].Enzyme and Microbial Technology,2016,84(10):1-10.
[21] RIZZI M,STYLOS P,RIEK A,et al.A kinetic study of immobilized lipase catalysing the synthesis of isoamyl acetate by transesterification in n-hexane[J].Enzyme and Microbial Technology,1992,14(9):709-714.
[22] KAMBLE M P,SHINDE S D,YADAV G D.Kinetic resolution of(R,S)-α-tetralol catalyzed by crosslinked Candida antarctica lipase B enzyme supported on mesocellular foam:a nanoscale enzyme reactor approach[J].Journal of Molecular Catalysis B:Enzymatic,2016,132:61-66.
[23] BADGUJAR K C,BHANAGE B M.Synthesis of geranyl acetate in non-aqueous media using immobilized Pseudomonas cepacia lipase on biodegradable polymer film:kinetic modelling and chain length effect study[J].Process Biochemistry,2014,49(8):1304-1313.
[24]GARCÍA R,GARCÍA T,MARTÍNEZ M,et al.Kinetic modelling of the synthesis of 2-hydroxy-5-hexenyl 2-chlorobutyrate ester by an immobilised lipase[J].Biochemical Engineering Journal,2000,5(3):185-190.
[25] YADAV G D,TRIVEDI A H.Kinetic modeling of immobilized-lipase catalyzed transesterification of n-octanol with vinyl acetate in non-aqueous media[J].Enzyme and Microbial Technology,2003,32(7):783-789.
[26] YADAV G D,BORKAR I V.Kinetic modeling of immobilized lipase catalysis in synthesis of n-butyl levulinate[J].Industrial & Engineering Chemistry Research,2008,47(10):3358-3363.
[27] SUN Jingcan,YU Bin,Philip Curran,et al.Lipase-catalysed ester synthesis in solvent-free oil system:is it esterification or transesterification[J].Food Chemistry,2013,141(3):2828-2832.
[28] KUPERKAR V V,LADE V G,PRAKASH A,et al.Synthesis of isobutyl propionate using immobilized lipase in a solvent free system:optimization and kinetic studies[J].Journal of Molecular Catalysis B:Enzymatic,2014,99:143-149.
[29] BERKA R M,SCHNEIDER P,GOLIGHTLY E J,et al.Characterization of the gene encoding an extracellular laccase of Myceliophthora thermophila and analysis of the recombinant enzyme expressed in Aspergillus oryzae[J].Applied and Environmental Microbiology,1997,63(8):3151-3157.
[30] HERTER S,MICHALIK D,MIKOLASCH A,et al.Laccase-mediated synthesis of 2-methoxy-3-methyl-5-(alkylamino)and 3-methyl-2,5-bis(alkylamino)-[1,4]-benzoquinones[J].Journal of Molecular Catalysis B:Enzymatic,2013,90:91-97.
[31] HAGHBEEN K,TAN Engwui,et al.Facile synthesis of catechol azo dyes[J].Journal of Organic Chemistry,1997,63:4503-4505.
[32] NIEDERMEYER T H J,MIKOLASCH A,LALK M.Nuclear amination catalyzed by fungal laccases:reaction products of p-hydroquinones and primary aromatic amines[J].Journal of Organic Chemistry,2005,70:2002-2008.
[33] MIKOLASCH A,MATTHIES A,LALK M,et al.Laccase-induced C-N coupling of substituted p-hydroquinones with p-aminobenzoic acid in comparison with known chemical routes[J].Applied Microbiology and Biotechnology,2008,80(3):389.
[34] BADGUJAR K C,BHANAGE B M.The green metric evaluation and synthesis of diesel-blend compounds from biomass derived levulinic acid in supercritical carbon dioxide[J].Biomass and Bioenergy,2016,84:12-21.

备注/Memo

备注/Memo:
收稿日期:2022-02-03
基金项目:国家自然科学基金(21546004,21576145)资助项目.
通信作者:王繁业(1964—),男,山东青岛人,教授,主要从事生物制药研究.E-mail:lwz_618@163.com
更新日期/Last Update: 2022-05-25