材料介导细胞固定化技术在生物发酵中的应用

doi:10.16085/j.issn.1000-6613.2020-1587

化工进展 ›› 2021, Vol. 40 ›› Issue (7): 3923-3931.DOI: 10.16085/j.issn.1000-6613.2020-1587

材料介导细胞固定化技术在生物发酵中的应用

高豪¹(), 陆家声¹, 章文明¹^,², 董维亮¹^,², 方艳¹^,², 余子夷³, 信丰学¹^,²(), 姜岷¹^,²()

^1.南京工业大学生物与制药工程学院，材料化学工程国家重点实验室，江苏南京 211816
^2.南京工业大学，江苏先进生物与化学制造协同创新中心（SICAM），江苏南京 211816
^3.南京工业大学化工学院，江苏南京 211816

收稿日期:2020-08-10 修回日期:2020-10-20 出版日期:2021-07-06 发布日期:2021-07-19
通讯作者: 信丰学,姜岷
作者简介:高豪（1995—），男，博士研究生，研究方向为合成生物学、生物催化剂固定化技术。E-mail：201861118033@njtech.edu.cn。
基金资助:
国家重点研发计划“合成生物学”重点专项(2018YFA0902200);国家自然科学基金(31961133017)

Application of material-mediated cell immobilization technology in biological fermentation

GAO Hao¹(), LU Jiasheng¹, ZHANG Wenming¹^,², DONG Weiliang¹^,², FANG Yan¹^,², YU Ziyi³, XIN Fengxue¹^,²(), JIANG Min¹^,²()

^1.State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, Jiangsu, China
^2.Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, Nanjing 211816, Jiangsu, China
^3.Institute of Chemical Industry, Nanjing Tech University, Nanjing 211816, Jiangsu, China

Received:2020-08-10 Revised:2020-10-20 Online:2021-07-06 Published:2021-07-19
Contact: XIN Fengxue,JIANG Min

摘要/Abstract

摘要：

细胞固定化技术具有高效、反应操作简便、能长时间保持细胞活力且可反复利用、稳定性好、耐受性强等优点，在生物发酵等领域显示出巨大的应用潜力。本文介绍了近年来高分子载体材料、无机载体材料和复合载体材料的细胞固定化技术在生物发酵领域的研究进展，分析了不同材料介导固定化细胞在复杂的环境，如低或高pH、毒性底物和高浓度产物等条件下与游离细胞生长代谢性能差异；并阐述了新型高分子膜材料（中空纤维膜和微米/纳米纤维膜）作为载体在生物发酵中的优势和应用；最后展望了通过设计新型优良聚合物载体来实现人工混菌体系在生物发酵中的可控性和鲁棒性。材料作为生物与非生物中物质界面上的活性和可调成分，为细胞提供了适宜的微环境，在生物发酵领域将得到更广泛应用。

关键词: 固定化, 多细胞, 生物反应器, 发酵, 膜材料

Abstract:

Cell immobilization technology, characterized by its high efficiency, simple reaction operation, long-term cell viability, repeatability, good stability and high tolerance, has shown great application potential in the field of biological fermentation industry. In this paper, the research progress of polymer carrier materials, inorganic carrier materials and composite carrier materials in the field of biological fermentation was reviewed. The differences in growth metabolic property between free and immobilized cells in a complex environment, such as low or high pH, toxic substrate and high concentration products were analyzed. In addition, the advantages and applications of new polymer membrane materials (hollow fiber membrane and micro/nano fiber membrane) as carriers in biological fermentation were also described. Finally, the controllability and robustness of the artificial microbial system in biological fermentation were prospected by designing excellent polymer carriers. The results showed that materials as active and tunable components at the interface of living and nonliving matter offer a suitable microenvironment for cells, which will be more widely used in the field of biological fermentation in the future.

Key words: immobilization, multicellular, bioreactor, fermentation, membrane material

中图分类号:

高豪, 陆家声, 章文明, 董维亮, 方艳, 余子夷, 信丰学, 姜岷. 材料介导细胞固定化技术在生物发酵中的应用[J]. 化工进展, 2021, 40(7): 3923-3931.

GAO Hao, LU Jiasheng, ZHANG Wenming, DONG Weiliang, FANG Yan, YU Ziyi, XIN Fengxue, JIANG Min. Application of material-mediated cell immobilization technology in biological fermentation[J]. Chemical Industry and Engineering Progress, 2021, 40(7): 3923-3931.

图/表 8

参考文献 46

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材料	菌株	固定化方法	产物	结果	参考文献
海藻酸钙凝胶	C. thermocellum C. thermolacticum	包埋	乙醇	乙醇的产率接近理论效率的85%	［6］
海藻酸钙凝胶	Candida shehatae Saccharomyces cerevisiae	包埋	乙醇	发酵时间缩短16.67%，乙醇产量提高了12.12%	［12］
果胶酸钙凝胶	L. casei	包埋	乳酸	乳酸的转化率为94.37%，乳酸的产量为32.95g·L^-1	［7］
壳聚糖凝胶	Enterococcus faecalis	包埋	L-瓜氨酸	建立了L-瓜氨酸工业生产工艺	［8］
海藻酸钠-壳聚糖凝胶	S. cerevisiae P. tannophilus	包埋	乙醇	凝胶稳定，乙醇浓度为20.04g·L^-1	［10］
海藻酸钙凝胶珠	L. rhamnosus	包埋	酸	优化了最佳的固定化条件	［13］

材料	菌株	固定化方法	产物	结果	参考文献
海藻酸钙凝胶	C. thermocellum C. thermolacticum	包埋	乙醇	乙醇的产率接近理论效率的85%	［6］
海藻酸钙凝胶	Candida shehatae Saccharomyces cerevisiae	包埋	乙醇	发酵时间缩短16.67%，乙醇产量提高了12.12%	［12］
果胶酸钙凝胶	L. casei	包埋	乳酸	乳酸的转化率为94.37%，乳酸的产量为32.95g·L^-1	［7］
壳聚糖凝胶	Enterococcus faecalis	包埋	L-瓜氨酸	建立了L-瓜氨酸工业生产工艺	［8］
海藻酸钠-壳聚糖凝胶	S. cerevisiae P. tannophilus	包埋	乙醇	凝胶稳定，乙醇浓度为20.04g·L^-1	［10］
海藻酸钙凝胶珠	L. rhamnosus	包埋	酸	优化了最佳的固定化条件	［13］

材料	菌株	固定化方法	产物	结果	参考文献
聚酰胺（尼龙）	P. acidipropionici	吸附	丙酸	丙酸生产强度和产量分别为0.46g·L^-1·h^-1和25.8g·L^-1	［14］
聚乙烯醇凝胶	C. acetobutylicum	包埋	丁醇	丁醇生产强度达0.57g·L^-1·h^-1	［17］
聚丙烯酰胺凝胶	L. rhamnosus	包埋	乳酸	凝胶具有良好的渗透特性，细胞完全保留在聚合物凝胶中	［18］
聚乳酸微管阵列膜	Lb. acidophilus	包埋	乳酸	包埋效率高、稳定性好	［19］
聚乙烯醇水凝胶	C. butyricum	包埋	1，3-丙二醇	稳定性好，生产强度提高	［20］
聚乙烯醇水凝胶	Zymomonas mobilis	包埋	乙醇	乙醇产量提高100%（31.09g·L^-1·h^-1）	［21］
聚丙烯酰胺凝胶	L. rhamnosus	包埋	乳酸	产物转化率为85%~90%	［22］

材料	菌株	固定化方法	产物	结果	参考文献
聚酰胺（尼龙）	P. acidipropionici	吸附	丙酸	丙酸生产强度和产量分别为0.46g·L^-1·h^-1和25.8g·L^-1	［14］
聚乙烯醇凝胶	C. acetobutylicum	包埋	丁醇	丁醇生产强度达0.57g·L^-1·h^-1	［17］
聚丙烯酰胺凝胶	L. rhamnosus	包埋	乳酸	凝胶具有良好的渗透特性，细胞完全保留在聚合物凝胶中	［18］
聚乳酸微管阵列膜	Lb. acidophilus	包埋	乳酸	包埋效率高、稳定性好	［19］
聚乙烯醇水凝胶	C. butyricum	包埋	1，3-丙二醇	稳定性好，生产强度提高	［20］
聚乙烯醇水凝胶	Zymomonas mobilis	包埋	乙醇	乙醇产量提高100%（31.09g·L^-1·h^-1）	［21］
聚丙烯酰胺凝胶	L. rhamnosus	包埋	乳酸	产物转化率为85%~90%	［22］

材料	菌株	固定化方法	产物	结果	参考文献
活性炭	C. acetobutylicum	吸附	氢和丁醇	生物膜的形成强化了氢气和丁醇的发酵	［24］
氧化铁纳米颗粒	Bacillus subtilis natto	吸附	甲萘醌-7	产率提高15%，颗粒的细菌捕获效率达到95%	［30］
陶瓷	Klebsiella pneumoniae	吸附	1,3-丙二醇	产率提高200%，细胞抗极端条件下有较高的耐受性	［31］
介孔氧化硅	L. rhamnosus	吸附	乳酸	葡萄糖转化率达92.4%	［32］

材料介导细胞固定化技术在生物发酵中的应用

Application of material-mediated cell immobilization technology in biological fermentation

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材料	菌株	固定化方法	产物	结果	参考文献
聚乙烯醇/海藻酸钙珠	L. rhamnosus	包埋	乳酸	乳酸最高生产强度为0.8g·L^-1·h^-1	［34］
纤维素/海藻酸钙/聚乳酸	L. bulgaricus	吸附/包埋	乳酸	在同一生物反应器发酵中避免抑制问题	［35］
二氧化硅/海藻酸钙	Oenococcus oeni	包埋	苹果酸	有效地避免产物抑制	［36］
聚乙烯醇/海藻酸钙	L. pentosus	包埋	乳酸	15次分批重复发酵中保持稳定高效的性能	［37］

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