高黏性蛋白材料的合成生物学及应用

doi:10.12211/2096-8280.2025-043

合成生物学 ›› 2025, Vol. 6 ›› Issue (4): 806-828.DOI: 10.12211/2096-8280.2025-043

高黏性蛋白材料的合成生物学及应用

李全飞¹^,², 陈乾¹^,², 刘浩¹^,², 贺坤东¹^,², 潘亮¹^,², 雷鹏¹^,², 谷益安¹^,², 孙良¹^,², 李莎¹^,², 邱溢彬¹^,², 王瑞¹^,², 徐虹¹^,²

^1.南京工业大学食品与轻工学院，江苏南京 210009
^2.材料化学工程全国重点实验室，江苏南京 210009

收稿日期:2025-05-08 修回日期:2025-07-02 出版日期:2025-08-31 发布日期:2025-09-03
通讯作者: 王瑞
作者简介:李全飞（1998—），男，博士研究生。研究方向为高黏性蛋白的生物合成及分离纯化。 E-mail：202462218257@njtech.edu.cn
王瑞（1987—），男，教授，博士生导师。研究方向为高性能蛋白材料合成生物学与应用。 E-mail：ruiwang2013@njtech.edu.cn
基金资助:
国家自然科学基金面上项目(22478185);江苏省合成生物学基础研究中心项目(BK20233003);南京工业大学材料化学工程全国重点实验室项目(KL-MCE-22A05);南京工业大学材料化学工程全国重点实验室项目(SKL-MCE-23A17)

Synthetic biology and applications of high-adhesion protein materials

LI Quanfei¹^,², CHEN Qian¹^,², LIU Hao¹^,², HE Kundong¹^,², PAN Liang¹^,², LEI Peng¹^,², GU Yi’an¹^,², SUN Liang¹^,², LI Sha¹^,², QIU Yibin¹^,², WANG Rui¹^,², XU Hong¹^,²

^1.College of Food Science and Light Industry，Nanjing University of Technology，Nanjing 210009，Jiangsu，China
^2.State Key Laboratory of Materials-oriented Chemical Engineering，Nanjing 210009，Jiangsu，China

Received:2025-05-08 Revised:2025-07-02 Online:2025-08-31 Published:2025-09-03
Contact: WANG Rui

摘要/Abstract

摘要：

高黏性蛋白材料因其卓越的生物黏附性和潜在的生物相容性，在生物医用材料和黏合剂领域展现出巨大的应用潜力。然而，传统方式获取的高黏蛋白材料面临诸多挑战，如产量低、结构复杂、难以规模化生产等。合成生物学作为新兴的交叉学科，为解决这些瓶颈提供了创新策略。本综述系统总结了近年来高黏性蛋白材料的生物合成、改性及应用进展，重点突出了合成生物学在解决高黏性蛋白材料产量、可控性以及功能多样性等方面的优势。全面梳理了基因工程实现对贻贝黏蛋白、藤壶胶蛋白和扇贝足丝蛋白等黏附蛋白的精确设计和高效表达，从而克服高黏蛋白材料在产量和可控性方面的限制。同时，综述了这些蛋白材料在生物黏合剂和医用功能涂层方面的独特优势，如贻贝蛋白的湿面黏附性、藤壶胶蛋白的强黏附性以及类弹性蛋白的可调控性。通过合成生物学方法，可以突破高黏蛋白材料在产量、性能和功能方面的限制，加速其在组织工程、表界面改性等领域的应用。最后，总结了当前合成生物学在高黏蛋白材料领域的最新进展和创新点，并展望了其未来的发展方向，为开发高性能、多功能的高黏蛋白材料提供了新的思路和策略。

关键词: 高黏性蛋白, 生物黏合剂, 功能涂层, 合成生物学

Abstract:

Due to their exceptional bioadhesive properties and potential biocompatibility, high-viscosity protein materials exhibit significant application prospects in the fields of biomedical materials and adhesives. However, traditionally sourced high-viscosity protein materials encounter numerous challenges, including low yields, structural complexity, and difficulties in scaling up production. Synthetic biology, as an emerging interdisciplinary field, offers innovative strategies to address these bottlenecks. This review systematically summarizes recent advances in the biosynthesis, modification, and applications of high-viscosity protein materials, focusing on the advantages of synthetic biology in addressing issues related to the yield, controllability, and functional diversity of these materials. The precise design and efficient expression of adhesive proteins, such as mussel adhesive proteins, barnacle cement proteins, and scallop foot proteins, achieved through genetic engineering, are comprehensively reviewed, demonstrating the overcoming of limitations in the production and controllability of high-viscosity protein materials. Furthermore, the unique advantages of these protein materials in bioadhesives and functional medical coatings, such as the wet adhesion of mussel proteins, the strong adhesion of barnacle cement proteins, and the tunable properties of elastin-like proteins, are summarized. By employing synthetic biology approaches, limitations in the yield, performance, and functionality of high-viscosity protein materials can be overcome, thereby accelerating their application in areas such as tissue engineering and surface modification. Finally, the latest advancements and innovations in the field of synthetic biology for high-viscosity protein materials are summarized, and future development directions are envisioned, offering new ideas and strategies for the development of high-performance, multifunctional high-viscosity protein materials. {L-End}

Key words: high-adhesion proteins, bioadhesives, functional coatings, synthetic biology

中图分类号:

Q816

李全飞, 陈乾, 刘浩, 贺坤东, 潘亮, 雷鹏, 谷益安, 孙良, 李莎, 邱溢彬, 王瑞, 徐虹. 高黏性蛋白材料的合成生物学及应用[J]. 合成生物学, 2025, 6(4): 806-828.

LI Quanfei, CHEN Qian, LIU Hao, HE Kundong, PAN Liang, LEI Peng, GU Yi’an, SUN Liang, LI Sha, QIU Yibin, WANG Rui, XU Hong. Synthetic biology and applications of high-adhesion protein materials[J]. Synthetic Biology Journal, 2025, 6(4): 806-828.

图/表 7

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宿主细胞	优点	缺点	适用性
大肠杆菌	生长快速，培养成本低廉，遗传背景清晰，易于基因操作	缺乏真核细胞的翻译后修饰机制，容易形成包涵体，可能导致蛋白活性降低	适用于表达结构简单、不需要复杂翻译后修饰的蛋白
枯草芽孢杆菌	分泌表达能力强，有利于蛋白的正确折叠，无内毒素污染	蛋白酶含量高，可能导致目的蛋白降解	适用于表达分泌蛋白
酿酒酵母/毕赤酵母	真核表达系统，能够进行一些简单的翻译后修饰，分泌表达能力较强	糖基化修饰可能与人源蛋白不同	适用于表达高分子量的、需要糖基化的蛋白
动物细胞	能够进行完整的翻译后修饰，保证蛋白的正确折叠和生物活性	生长速度较慢，培养成本很高，容易受到病毒污染	适用于表达需要复杂糖基化修饰的蛋白，例如抗体和治疗性蛋白
植物细胞	培养成本低廉，易于大规模培养，安全性高	翻译后修饰能力有限，表达水平相对较低	适用于表达一些结构简单的蛋白，或者用于大规模生产

宿主细胞	优点	缺点	适用性
大肠杆菌	生长快速，培养成本低廉，遗传背景清晰，易于基因操作	缺乏真核细胞的翻译后修饰机制，容易形成包涵体，可能导致蛋白活性降低	适用于表达结构简单、不需要复杂翻译后修饰的蛋白
枯草芽孢杆菌	分泌表达能力强，有利于蛋白的正确折叠，无内毒素污染	蛋白酶含量高，可能导致目的蛋白降解	适用于表达分泌蛋白
酿酒酵母/毕赤酵母	真核表达系统，能够进行一些简单的翻译后修饰，分泌表达能力较强	糖基化修饰可能与人源蛋白不同	适用于表达高分子量的、需要糖基化的蛋白
动物细胞	能够进行完整的翻译后修饰，保证蛋白的正确折叠和生物活性	生长速度较慢，培养成本很高，容易受到病毒污染	适用于表达需要复杂糖基化修饰的蛋白，例如抗体和治疗性蛋白
植物细胞	培养成本低廉，易于大规模培养，安全性高	翻译后修饰能力有限，表达水平相对较低	适用于表达一些结构简单的蛋白，或者用于大规模生产

纯化方法	原理	优点	缺点
亲和色谱	基于目标蛋白与特定配体（如抗体、金属离子、辅酶等）之间的高特异性结合	高特异性、高纯度、操作简便	可能需要添加标签，洗脱条件可能较为苛刻，某些配体价格昂贵
离子交换色谱	基于目标蛋白与固定化的带电基团之间的静电相互作用	适用于大规模纯化，成本较低	特异性不如亲和色谱，需要优化洗脱条件
凝胶过滤色谱	基于目标蛋白的分子大小进行分离	操作简便，可以确定蛋白的分子量	分辨率较低，不适用于分离分子量相近的蛋白
疏水相互作用色谱	基于目标蛋白表面的疏水性与固定化的疏水基团之间的相互作用	适用于分离疏水性蛋白	需要优化盐浓度和洗脱条件
超滤/透析	利用半透膜对分子大小的截留作用	操作简便，适用于大规模处理	不能分离分子大小相近的蛋白
沉淀法	通过改变溶液的条件（如盐浓度、pH 值、温度等），使目标蛋白溶解度降低，从而沉淀析出	成本低廉，适用于大规模初步纯化	特异性较低，可能需要后续的精细纯化

纯化方法	原理	优点	缺点
亲和色谱	基于目标蛋白与特定配体（如抗体、金属离子、辅酶等）之间的高特异性结合	高特异性、高纯度、操作简便	可能需要添加标签，洗脱条件可能较为苛刻，某些配体价格昂贵
离子交换色谱	基于目标蛋白与固定化的带电基团之间的静电相互作用	适用于大规模纯化，成本较低	特异性不如亲和色谱，需要优化洗脱条件
凝胶过滤色谱	基于目标蛋白的分子大小进行分离	操作简便，可以确定蛋白的分子量	分辨率较低，不适用于分离分子量相近的蛋白
疏水相互作用色谱	基于目标蛋白表面的疏水性与固定化的疏水基团之间的相互作用	适用于分离疏水性蛋白	需要优化盐浓度和洗脱条件
超滤/透析	利用半透膜对分子大小的截留作用	操作简便，适用于大规模处理	不能分离分子大小相近的蛋白
沉淀法	通过改变溶液的条件（如盐浓度、pH 值、温度等），使目标蛋白溶解度降低，从而沉淀析出	成本低廉，适用于大规模初步纯化	特异性较低，可能需要后续的精细纯化

高黏性蛋白材料的合成生物学及应用

Synthetic biology and applications of high-adhesion protein materials

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