漆酶/脂肪酶催化制备丝裂霉素类似物及其响应面法优化

兰州理工大学学报 ›› 2022, Vol. 48 ›› Issue (3): 71-76.

漆酶/脂肪酶催化制备丝裂霉素类似物及其响应面法优化

薛晓, 李楷原, 刘翠, 邓雅姗, 许慧, 王繁业^*

青岛科技大学化工学院, 山东青岛 266042

收稿日期:2021-04-27 出版日期:2022-06-28 发布日期:2022-10-09
通讯作者: 王繁业(1964-),男,山东青岛人,研究员.Email:lwz_618@163.com
基金资助:
国家自然科学基金(21546004,21576145)

Preparation of mitomycin analogs mediated by laccase/lipase and optimization using response surface method

XUE Xiao, LI Kai-yuan, LIU Cui, DENG Ya-shan, XU Hui, WANG Fan-ye

College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China

Received:2021-04-27 Online:2022-06-28 Published:2022-10-09

摘要/Abstract

摘要： 丝裂霉素及其类似物,广泛应用于各种肿瘤.为了获得优异的产率和环境友好性,采用一锅法工艺,以漆酶/脂肪酶为催化剂,催化2-甲基苯-1,4-二酚与正丁胺的多米诺反应制备丝裂霉素类似物2-丁胺-3-甲基-1,4-苯醌(c).采用响应面技术优化了反应条件:2-甲基苯-1,4-二酚与胺的物质的量比为1.16∶1、漆酶与脂肪酶的活性比为1.14∶2、反应温度为38.9 ℃,最佳产率达到87.17%.建立了产率模型,该模型考虑了2-甲基苯-1,4-二酚与胺的物质的量比、漆酶与脂肪酶活性比和反应温度对产率的影响,可以准确的预测产率(R²为0.994 1).漆酶/脂肪酶协同催化体系一锅法合成丝裂霉素类似物,显著提高了产率,可作为提高丝裂霉素类似物产率的绿色替代工艺.

关键词: 脂肪酶, 响应面优化, 漆酶, 丝裂霉素类似物

Abstract: Mitomycins and its analogs have been widely used for treating various tumors. In order to obtain excellent yield and environmental friendliness, an efficient one-pot process for the synthesis of 2-(butylamino)-3-methyl-1, 4-benzoquinone (c), a mitomycin-like compound by the domino reaction of 2-methylbenzene-1, 4-diol and butylamine using laccase/lipase as co-catalysts, has been developed. In the work, the process proposed here was improved by optimizing the relevant factors using the response surface methodology. The optimum conditions were obtained as follows: molar ratio of 2-methylbenzene-1, 4-diol to amine was 1.16∶1, activity ratio of laccase to lipase was 1.14∶2 and reaction temperature was 38.9 ℃, in which the highest yield was 87.17%. The yield model was established, which considered the effects of the amount of 2-methylbenzene-1, 4-diol to amine, the activity ratio of laccase to lipase and the reaction temperature on the yield and could accurately predict the yield (R=0.994 1). The results obtained indicate that this process may be useful as a green alternative process forhigher yield production of mitomycin analogs.

Key words: lipase, response surface methodology, laccase, mitomycin-like compound

中图分类号:

TQ465.92

薛晓, 李楷原, 刘翠, 邓雅姗, 许慧, 王繁业. 漆酶/脂肪酶催化制备丝裂霉素类似物及其响应面法优化[J]. 兰州理工大学学报, 2022, 48(3): 71-76.

XUE Xiao, LI Kai-yuan, LIU Cui, DENG Ya-shan, XU Hui, WANG Fan-ye. Preparation of mitomycin analogs mediated by laccase/lipase and optimization using response surface method[J]. Journal of Lanzhou University of Technology, 2022, 48(3): 71-76.

参考文献

[1] EDEN W,KOK N,WOENSDREGT K,et al.Safety of intraperitoneal mitomycin C versus intraperitoneal oxaliplatin in patients with peritoneal carcinomatosis of colorectal cancer undergoing cytoreductive surgery and HIPEC [J].Eur J Surg Oncol,2018,44(2):220-227.
[2] VERWEIJ J,PINEDO H M,MITOMYCIN C.Mechanism of action,usefulness and limitations [J].Anti-cancer drugs,1990,1(1):5-14.
[3] NITHIANANDAM V S,ERHAN S.Quinone-amine polymers:18:A novel method for the synthesis of poly(alkyl aminoquinone)s - ScienceDirect [J].Polymer,1998,39(17):4095-4098.
[4] 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.
[5] HERTER S,DMICHALI K,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.
[6] WELLINGTON K W,STEENKAMP P,BRADY D.Diamination by N-coupling using a commercial laccase [J].Bioorganic & Medicinal Chemistry,2010,18(4):1406-1414.
[7] LÓPEZ-IGLESIAS M,GOTOR-FERNÁNDEZ V.Recent advances in biocatalytic promiscuity:hydrolase-catalyzed reactions fornonconventional transformations [J].Chemical Record,2015,15(4):743-759.
[8] DWIVEDEE B P,SONI S,SHARMA M,et al.Promiscuity of lipase-catalyzed reactions for organic synthesis:a recent update [J].Chemistryselect,2018,3(9):2441-2466.
[9] SUTEER A,WITAYAKRA N,ARTHU R,et al.Cocatalytic enzyme system for the michael addition reaction of in-situ-generated ortho-quinones [J].European Journal of Organic Chemistry,2009,3:358-363.
[10] MACIAS-SANCHEZ M,ROBLES-MEDINA A,JIMENEZ-CALLEJON M J,et al.Optimization of biodiesel production from wet microalgal biomass by direct transesterification using the surface response methodology [J].Renewable Energy,2018,129:141-149.
[11] EL-BOULIFI N,ARACIL J,MARTINEZ M.Optimization of lipase-catalyzed synthesis of diglycerol monooleate by response surface methodology [J].Biomass and Bioenergy,2014,61:179-186.
[12] ZHANG Y Y,LIU J H.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(11/12):909-912.
[13] MACELLARO G,PEZZELLA C,CICATIELLO P,et al.Fungal laccases degradation of endocrine disrupting compounds [J].Biomed Res Int,2014(3/4):614038-614046.
[14] SELVARAJ R,MOORTHY I G,KUMAR R V,et al.Microwave mediated production of FAME from waste cooking oil:Modelling and optimization of process parameters by RSM and ANN approach [J].Fuel,2018,237:40-49.
[15] AMIRIA S,SHAKERIA A,SOHRABIB M R,et al.Optimization of ultrasonic assisted extraction of fatty acids from Aesculus hippocastanum fruit by response surface methodology [J].Food Chemistry,2019,271:762-766.
[16] GOVIND V,WAGHMAR E.Kinetics of enzymatic synthesis of cinnamyl butyrate by immobilized lipase [J].Applied Biochemistry and Biotechnology,2017,183(3):792-806.
[17] KIM Y J,NICELL J A.Laccase-catalysed oxidation of aqueous triclosan [J].Journal of Chemical Technology & Biotechnology,2010,81(8):1344-1352.
[18] DHAKE K P,TAMBADE P J,QURESHI Z S,et al.HPMC-PVA film immobilized rhizopus oryzae lipase as a biocatalyst for transesterification reaction [J].ACS Catalysis,2011,1(4):316-322.
[19] DEMIRANDA A S,MIRANDA L S M,DESOUZA R O M A.Lipases:valuable catalysts for dynamic kinetic resolutions [J].Biotechnology Advances,2015,33(5):372-393.
[20] MATHPATI A C,BADGUJAR K C,BHANAGE B M.Kinetic modeling and docking study of immobilized lipase catalyzed synthesis of furfuryl acetate [J].Enzyme & Microbial Technology,2016,84:1-10.
[21] LIESE A,HILTERHAUS L.Evaluation of immobilized enzymes for industrial applications [J].Chemical Society Reviews,2013,42:6236-6249.
[22] ČESNI K,SUDAR M,VASIĆ-RAČKI M,et al.Book of abstracts [M].Budapest,Hungary:Hungarian Chemical Society,2017.
[23] ROCHA-MARTIN J,VELASCO-LOZANO S,GUISÁN J M,et al.Oxidation of phenolic compounds catalyzed by immobilized multi-enzyme systems with integrated hydrogen peroxide production [J].Green Chemistry,2013,16:303-311.
[24] JI Q,WANG B,TAN J,et al.Immobilized multienzymatic systems for catalysis of cascade reactions [J].Process Biochemistry,2016,51(9):1193-1203.
[25] XU Y,LI F,YANG K,et al.A facile and robust non-natural three enzyme biocatalytic cascade based on Escherichia coli surface assembly for fatty alcohol production [J].Energy Conversion and Management,2019,181:501-506.
[26] GHASEMI S,HEIDARY M,FARAMARZI M A,et al.Immobilization of lipase on Fe₃O₄/ZnO core/shell magnetic nanoparticles and catalysis of Michael-type addition to chalcone derivatives [J].Journal of Molecular Catalysis B Enzymatic,2014,100:121-128.
[27] YUAN Y,YANG L,LIU S,et al.Enzyme-catalyzed Michael addition for the synthesis of warfarin and its determination via fluorescence quenching of l-tryptophan [J].Spectrochimica Acta Part A Molecular & Biomolecular Spectroscopy,2017,176:183-188.
[28] SOUZA R,MATOS L,GONALVES K M,et al.Michael additions of primary and secondary amines to acrylonitrile catalyzed by lipases [J].Tetrahedron Letters,2009,50(17):2017-2018.
[29] 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.