王义翘先生和BPEC对生物化学工程发展的巨大作用  

Great impact of Professor Daniel I.C.Wang and BPEC on development of biochemical engineering

作　　者：苏志国[1] SU Zhiguo(The State Key Laboratory of Biochemical Engineering,Institute of Process Engineering,Chinese Academy of Sciences,Beijing 100190,China)

机构地区：[1]中国科学院过程工程研究所生化工程国家重点实验室,北京100190

出　　处：《合成生物学》2021年第4期470-481,共12页Synthetic Biology Journal

基　　金：国家自然科学基金(21821005)。

摘　　要：王义翘先生是美国麻省理工学院生物技术过程工程中心(BPEC)的创始人。在他的领导下,BPEC通过协同创新和生物化学工程(生化工程)的前沿探索,取得了显著的成就。(1)引领了生化工程进入生物制药新时代。与最初的生化工程概念相比,BPEC的重点发生了很大的转变,目标分子不再局限于抗生素、化学品和燃料等小分子,而是拓展到抗体、细胞因子、血液蛋白质和疫苗抗原等生物大分子,解决这些生物药品大规模生产所遇到的工程科学问题。(2)开启了动物细胞培养工程。当细胞生物学家忙于通过增加滚瓶的数量来扩大生产时,BPEC通过流体力学和传质分析,最大限度地减少剪切应力和扩散限制,成功地实现了动物细胞的生物反应器培养,设计出大规模培养的最佳培养基组成和添加策略,获得了蛋白质翻译后修饰随时间变化的规律,提高了动物细胞反应器的目标蛋白质产量。(3)创新了高质量生物大分子的分离纯化技术,建立了亲和膜、反胶束、电辅助分离等新方法。利用准弹性光散射技术,研究了蛋白质的再折叠和聚集机制,发明了聚乙二醇稳定再折叠中间体的新技术。(4)建立了生化工程协同创新和人才培养体系,促进了BPEC成员之间密切合作和与生物技术企业的密切合作,吸引和培养了众多在生化工程领域有建树的年轻人才。本文还对王义翘先生和BPEC对我国生化工程发展的启示和借鉴做了简要的评述。Professor Daniel I.C.Wang was the founder of the Biotechnology Process Engineering Center(BPEC)at Massachusetts Institute of Technology(MIT).Under his leadership,BPEC has made remarkable achievements.It is a historical monument with great influence on the development of biochemical engineering.The historical background outstanding contributions,innovative mechanisms,and significant impact of BPEC,led by Prof.Wang,were reviewed in this paper.(1)Leading biochemical engineering into a new era of biopharmaceuticals.With the development of genetic engineering in the 1970-1980s,a new era of modern biopharmaceuticals emerged.Professor Wang acutely felt that the production of biomacromolecule medicines by genetic engineering must solve a series of engineering science problems,which was the opportunity and challenge of biochemical engineering.He proposed to the National Science Foundation of the United States(NSF)for establishing BPEC at MIT.It was approved by the NSF in 1985.Compared with the initial concept of biochemical engineering at that time,the focus of BPEC had a great shift.The target molecules were no longer limited to microbial fermentation or bioconversion of antibiotics,chemicals and fuels.The mission of BPEC was to solve the engineering problems encountered by the large-scale production of various protein pharmaceuticals.In doing so,BPEC has successfully led biochemical engineering into the new era of biopharmaceuticals and established a unique position in the development of modern biotechnology.(2)Launching animal cell culture engineering.Animal cell culture is required for production of very complex biomacromolecules.While cell biologists were busy to scale up production by increasing the number of roller bottles,BPEC started engineering approach by design of bioreactors and control strategies.Successful bioreactor cultivation of mammalian cells was realized by minimization of shear stress and diffusion limitation.The culture nutritional composition was optimized by stoichiometric calculation.The strategy

关 键 词：生化工程 生物制药 生物反应器 生化分离工程 生化制剂工程 

分 类 号：Q819[生物学—生物工程]