合成生物学 ›› 2021, Vol. 2 ›› Issue (4): 528-542.DOI: 10.12211/2096-8280.2020-091

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人造蛋白功能材料的生物合成及应用

曾丹1, 储建林2, 陈燕茹1, 范代娣1   

  1. 1.西北大学化工学院,陕西省可降解生物医用材料重点实验室,陕西省生物材料与发酵工程技术研究中心,陕西 西安 710069
    2.南京工业大学药学院,江苏 南京 210000
  • 收稿日期:2020-12-28 修回日期:2021-05-29 出版日期:2021-08-31 发布日期:2021-09-10
  • 通讯作者: 范代娣
  • 作者简介:曾丹(1989—),女,博士,副教授。主要研究方向为生物医用材料。E-mail:zengdan0301@nwu.edu.cn|范代娣(1965—),女,博士,教授。主要研究方向为可降解生物材料,预防医学和营养医学。E-mail:fandaidi@nwu.edu.cn
  • 基金资助:
    国家重点研发计划“合成生物学”重点专项;人造蛋白质合成的细胞设计构建及应用(2019YFA0905200)

Biological synthesis and applications of artificial protein functional materials

Dan ZENG1, Jianlin CHU2, Yanru CHEN1, Daidi FAN1   

  1. 1.School of Chemical Engineering,Shaanxi Key Laboratory of Degradable Biomedical Materials,Shaanxi R&D Center of Biomaterials and Fermentation Engineering,Northwest University,Xi’an 710069,Shaanxi,China
    2.School of Pharmacy,Nanjing University of Technology,Nanjing 210000,Jiangsu,China
  • Received:2020-12-28 Revised:2021-05-29 Online:2021-08-31 Published:2021-09-10
  • Contact: Daidi FAN

摘要:

人造蛋白功能材料具有良好的生物相容性和生物可降解性,来源广泛且功能多样,是一类理想的生物材料,在生物工程、医药、军事和纺织等领域具有广泛的应用前景。然而,现阶段蛋白功能材料的微生物合成仍存在表达量低、性能不稳定等问题,严重限制了这些蛋白材料的高效生产与应用。合成生物学在工程化理念的指导下,为人造蛋白功能材料提供了“精准设计—系统构建—调控表达—工程应用”的研究策略。本文介绍了蛛丝蛋白、蚕丝蛋白、类人胶原蛋白和贻贝蛋白等主要蛋白功能材料的生物合成研究进展,并阐述了人造蛋白细胞工厂的构建、蛋白的调控表达和其在组织工程材料等领域的应用现状。具有动态响应特性的人造蛋白功能材料是未来的研究方向。

关键词: 人造蛋白功能材料, 合成生物学, 细胞工厂, 表达调控, 工程应用

Abstract:

Artificial protein functional materials have good biocompatibility, biodegradability, broad resources of raw materials, and diverse functions. As ideal biological materials, they have a wide range of application prospects in bioengineering, medicine, military and textiles. However, microbial synthesis of protein functional materials still has problems such as low expression and unstable performance, which severely restrict their efficient production and application. In recent years, there is a trend of designing artificial protein functional materials that not only possess multi-functional properties but are biomimetic, adaptive and dynamically responsive to biological processes, and such a trend puts forward new requirements for the design and engineering control of macromolecular systems, which raise a necessity for developing research methods to assemble engineered protein molecules into functional macroscopic materials. Under the guidance of engineering concepts, synthetic biology provides a strategy for developing "precise design-system construction-regulatory expression-engineering application" for artificial protein functional materials. This review comments the research progress in the biological synthesis of major protein functional materials such as spider silk protein, silk protein, human-like collagen and mussel protein, and explores the construction of artificial protein cell factory, the regulation of protein expression and their applications as tissue engineering materials and other fields. In view of the current problems of poor biocompatibility and insufficient efficacy of clinical products, artificial protein functional materials can be assembled and processed according to functional requirements, and used to fabricate artificial tendons, artificial skin, degradable hemostatic materials, artificial bones and new protein material medical products such as high-viscosity anti-fouling coating products. There are still several challenges that need to be solved urgently: (1) There are few theoretical analysis tools and models at this stage, making the design, prediction and analysis of functional proteins relatively limited, and a more comprehensive protein database needs to be established; (2) There are many expression regulators in E. coli and other microbial systems, and adaptation for the design of expression elements and the target gene, the regulation of protein synthesis pathways and the systemic nature need to be studied to improve the efficiency of protein expression; (3) In terms of engineering applications, it is also necessary to comprehensively consider material stability and biological safety. Finally, the research direction is prospected, which provides insights for scholars working in related fields.

Key words: artificial protein functional materials, synthetic biology, cell factory, expression regulation, engineering applications

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