合成生物学

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生物制造的PE值与PX值:定义与应用

张以恒1,2, 陈雪梅2, 韩平平1,2   

  1. 1.低碳合成工程生物学全国重点实验室,中国科学院天津工业生物技术研究所,天津 300308
    2.中国科学院天津工业生物技术研究所体外合成生物学中心,天津 300308
  • 收稿日期:2025-03-20 修回日期:2025-04-29 出版日期:2025-05-12
  • 通讯作者: 张以恒
  • 作者简介:张以恒(1971—),低碳合成工程生物学全国重点实验室主任,中国科学院天津工业生物技术研究所体外合成生物学中心主任,曾经任美国弗吉尼亚理工大学终身正教授。他是体外合成生物学的奠基人之一与产业化领跑者,创建体外生物转化(ivBT)技术平台,率先提出“人工多酶分子机器”概念并实现产业化突破。在秸秆制粮、体外无细胞呼吸作用(无氧呼吸作用产氢、有氧呼吸作用制电)、人工合成淀粉、淀粉制塔格糖与肌醇等方向取得了一系列原创性突破。E-mail:zhang_xw@tib.cas.cn
  • 基金资助:
    科技部重点专项(2022YFA0912300);国家自然科学基金面上项目(NSFC 32271544);合成生物学海河实验室颠覆性创新项目(22HHSWSS000155);天津市合成生物技术创新能力提升行动项目(TSBICIP-CXRC-067)

PE and PX Values in Biomanufacturing: Definitions and Applications

ZHANG Yi-Heng P. Job1,2, CHEN Xuemei2, HAN Pingping1,2   

  1. 1.State Key Laboratory of Engineering Biology for Low-Carbon Manufacturing,Tianjin Institute of Industrial Biotechnology,Chinese Academy of Sciences,Tianjin 300308,China
    2.In vitro Synthetic Biology Center,Tianjin Institute of Industrial Biotechnology,Chinese Academy of Sciences,Tianjin 300308,China
  • Received:2025-03-20 Revised:2025-04-29 Online:2025-05-12
  • Contact: ZHANG Yi-Heng P. Job

摘要:

生物制造是战略新兴产业的典型代表,是生物经济的新质生产力。作者曾提出“道法术器”对工业生物制造的哲学指导意义。为进一步阐述生物制造中“术以立策”的原则,本文首次提出衡量生物催化剂(即“术”)水平的关键经济指标:PE值(Product-to-Enzyme Ratio)与PX值(Product-to-X(Cell) Ratio)。这两个指标具有简单、透明且量化的属性。PE值表示产品与非细胞催化剂(酶分子或多酶分子机器,以下简称“多酶机器”)的重量比值,也可通过技术指标总转换数(Total Turn-over Number,TTN)计算其理论值。PX值应用于细胞工厂发酵,表示产品与细胞催化剂的重量比。基于PE值与PX值,可以快速估算不同生物制造过程中的生物催化剂成本,进而指导降低降本增效的关键路径。作者汇总了生物制造的产业案例及文献数据,展示了酶分子及多酶机器PE值、细胞工厂PX值的特点。研究表明,淀粉酶水解淀粉的PE值是纤维素酶水解纤维素的50-100倍;在固态纤维素水解过程中,纤维素酶的超大用量是非粮生物质糖化与利用的最大经济障碍。最后,本文探讨了PE值的技术改进路径,特别是多酶共固定技术的潜力,并明确了工业酶皇冠——纤维素酶研究的新方向。PE值与PX值的分析将为生物制造战略新兴产业的发展提供了全新的视角,深化了对生物制造中关键“芯片”——生物催化剂成本的理解,为未来技术的发展提供重要参考与指导。

关键词: 生物制造, PE值, PX值, 道法术器, 多酶分子机器

Abstract:

Biomanufacturing is one of the representatives of strategic emerging industries and is a new quality productive force for the coming bioeconomy. The authors used to propose the philosophical guiding significance of "Tao-Fa-Shu-Qi" for industrial biomanufacturing. To further elaborate on the principle of "Shu is techniques" in biomanufacturing, for the first time this opinion paper introduces the new concepts of "Product-to-Enzyme Ratio" (abbreviated as PE value) that is the weight ratio of the product to the non-cell biocatalysts (i.e., enzyme(s)), such as enzyme molecules and multiple-enzyme molecular machines, and of "Product-to-X(Cell) Ratio" (abbreviated as PX value) that is the weight ratio of the product to cell mass. Both values feature simple, clear and quantitative properties. The PE value can be applied to enzyme-based biocatalysis or in vitro biotransformation; PX value can be applied to cell-based fermentation. Theoretical PE values can be calculated from total-turn-over number (TTN) of enzyme. First, the author defines and calculates the PE value. Second, authors summarize and classify industrial biomanufacturing cases and literature data catalyzed by enzymes, multiple-enzyme molecular machines, and cells. It was found that enzymatic starch-hydrolyzing enzymes has a PE value 50-100 times of that of enzymatic cellulose hydrolysis, resulting in an extremely high cellulase dosage. This ultra-high enzyme cost is the biggest obstacle to the industrialization of the second-generation biorefineries that are based on the biological conversion and utilization of lignocellulosic biomass. Lastly, the PE/PX values can be used to quickly estimate and compare the costs of biocatalysts, such as enzyme molecules, multiple-enzyme molecular machines, and microbial cells in the biomanufacturing process, guiding the development path for further decreasing the cost of biocatalysts. Increasing PE values by enzyme (co-)immobilization could greatly decrease biocatalyst costs, surpassing cell-based fermentation. Cellulase could be the largest industrial enzyme with a potential market size of 500 billion RMB by considering the huge supplies of non-food lignocellulosic biomass and potential markets of renewable biocommodities and artificial food/feed. The calculation and analysis of the PE/PX values would provide a new perspective for the future development of the strategic emerging industry of biomanufacturing, deepen the understanding of the cost of biocatalysts in biomanufacturing, promote the high-quality development of the bioeconomy, predict the future cost trend of biological products, and evaluate the industrialization potential of emerging biotechnologies.

Key words: biomanufacturing, PE value, PX value, Tao-Fa-Shu-Qi, multiple-enzyme molecular machine

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