Applications of protein engineering in pharmaceutical industry

WEN Yanhua; LIU Hedong; CAO Chunlai; WU Ruibo

doi:10.12211/2096-8280.2024-061

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Applications of protein engineering in pharmaceutical industry

Invited Review | 更新时间：2025-06-20

- Applications of protein engineering in pharmaceutical industry
- Synthetic Biology Journal Vol. 6, Issue 1, Pages: 65-86(2025)
- 作者机构：
  
  1.中山大学药学院，广东广州 510006
  2.珠海联邦制药股份有限公司，广东珠海 519040
  3.联邦生物科技（珠海横琴）有限公司，广东珠海 519031
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2024-061
  CLC： Q816
- Received：05 August 2024，
  
  Revised：2024-10-16，
  
  Published：31 January 2025
- 稿件说明：
移动端阅览
温艳华，刘合栋，曹春来，巫瑞波. 蛋白质工程在医药产业中的应用［J］. 合成生物学， 2025， 6（1）： 65-86

WEN Yanhua， LIU Hedong， CAO Chunlai， WU Ruibo. Applications of protein engineering in pharmaceutical industry［J］. Synthetic Biology Journal， 2025， 6（1）： 65-86
温艳华，刘合栋，曹春来，巫瑞波. 蛋白质工程在医药产业中的应用［J］. 合成生物学， 2025， 6（1）： 65-86 DOI： 10.12211/2096-8280.2024-061.

WEN Yanhua， LIU Hedong， CAO Chunlai， WU Ruibo. Applications of protein engineering in pharmaceutical industry［J］. Synthetic Biology Journal， 2025， 6（1）： 65-86 DOI： 10.12211/2096-8280.2024-061.

摘要

蛋白质工程，通过定向进化、半理性或理性设计、计算机辅助设计等手段，实现对蛋白质特定功能的设计和改造，获得的工程化蛋白质在食品、医药、能源、材料等行业具有重要的应用价值。在医药化工领域，工程化酶可作为化学原料药及其中间体合成的高效生物催化剂，实现医药工业绿色制造。在生物制药领域，多肽或蛋白修饰酶的改造可显著提升候选药物的制备效率，诊断酶的改造则可以大幅增强检测的准确性和灵敏度。此外，蛋白质工程在提升治疗性酶和治疗性抗体等生物制剂的生物活性、增强药物稳定性、降低免疫原性等方面也发挥重要作用，从而提高药物的可开发性、安全性和有效性。因此，本文简要回顾了蛋白质工程的发展历程，具体阐述了其在化学原料药合成和生物制药两大产业中的一系列应用实例，旨在剖析蛋白质工程在科技成果转化及医药产业应用中存在的问题与挑战，并展望医药产业中蛋白质工程的未来发展方向，以期为促进产学研一体化发展提供借鉴。

Abstract

Protein engineering performs specific designs and modifications on proteins through directed evolution

semi-rational or rational design

computer-assisted design

and so on. The engineered proteins

with improved properties

have significant applications in food

medicine

fuel

and material industries. For the chemical and pharmaceutical industry

engineered enzymes can serve as efficient biocatalysts for the synthesis of active pharmaceutical ingredients (API) and their intermediates

aligning with the concepts and principles of green chemistry and manufacturing. For the biopharmaceutical industry

the engineering of peptide or protein modifying enzymes can boost the efficiency in preparing drug candidates

while engineered diagnostic enzymes can make detection more accurate and sensitive. Moreover

protein engineering can improve the bioactivities of biological drugs such as therapeutic enzymes and antibodies

increase stability

and mitigate immunogenic response for their safety and efficacy. Here

we review the tremendous progress in protein engineering

elucidate its importance in the research and development of chemically derived drugs and biologics

and provide examples of its applications. These examples encompass the discovery of enzymes or antibodies

the process of protein engineering

and the subsequent economic advantages. We aim to showcase the practical implementation of protein engineering in the pharmaceutical industry and facilitate technology transfer

thereby fostering seamless integration between research

development

and industrial production. Furthermore

we discuss challenges such as cost-effectiveness and market changes in the synthesis of API

and multi-target optimization

long cycle and high risk in the discovery and development of biopharmaceuticals. Finally

we look forward to the prospects of protein engineering in pharmaceutical industry. In the future

automated pipelines consisting artificial intelligence and self-driving laboratories will accelerate the design-build-test-learn cycle

leading to rapid progress in molecular design and discovery.

关键词

Keywords

references

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