合成生物学

• 特约评述 •    

天冬氨酸族饲用氨基酸微生物细胞工厂的创制

赵欣雨, 盛琦, 刘开放, 刘佳, 刘立明   

  1. 江南大学生物工程学院,工业生物技术教育部重点实验室,江苏 无锡 214122
  • 收稿日期:2025-04-02 修回日期:2025-06-18 出版日期:2025-06-19
  • 通讯作者: 刘佳,刘立明
  • 作者简介:赵欣雨(2001—),女,硕士研究生。研究方向为微生物细胞工厂。E-mail:zxy_201710@163.com
    刘佳(1988—),女,高级实验师。研究方向为酶催化工程技术。E-mail:liujia@jiangnan.edu.cn
    刘立明(1976—),男,教授、博士生导师,教育部高层次人才。研究方向为合成生物学技术和微生物细胞工厂。E-mail:mingll@jiangnan.edu.cn
  • 基金资助:
    江苏省农业科技自主创新资金项目(CX(23)2005)

Construction of microbial cell factories for aspartate-family feed amino acids

ZHAO Xinyu, SHENG Qi, LIU Kaifang, LIU Jia, LIU Liming   

  1. Key Laboratory of Industrial Biotechnology,Ministry of Education,School of Biotechnology,Jiangnan University,Wuxi 214122,Jiangsu,China
  • Received:2025-04-02 Revised:2025-06-18 Online:2025-06-19
  • Contact: LIU Jia, LIU Liming

摘要:

氨基酸作为动物饲料的重要组成部分,是提高畜禽消化机能、禽肉品质、蛋白转化效率,降低豆粕使用量的关键要素。合成生物学技术的快速发展为氨基酸高产菌株构建和优化铺平了道路,极大地提升了氨基酸生产效率,显著降低了生产成本。本文在分析L-赖氨酸、L-甲硫氨酸、L-苏氨酸和L-异亮氨酸等四种天冬氨酸族氨基酸合成途径的基础上,详细介绍了菌种改造方法和策略,包括代谢路径重构、代谢途径优化、辅因子供应和增强产物外排等四个方面,并从工业环境抗逆性、底物利用范围的拓展以及动态调控系统的优化三个方面进行展望,以期为高性能氨基酸生产菌株的创制提供理论指导和技术支撑。

关键词: 天冬氨酸族氨基酸, 微生物细胞工厂, 代谢工程, 合成生物学, 基因编辑

Abstract:

Amino acids are crucial components of animal feed, playing key roles in improving digestive function in livestock, enhancing meat quality, increasing protein conversion efficiency, and reducing reliance on soybean meal. Driven by global population growth and dietary changes, the rising demand for animal protein has strained the livestock industry. This industry traditionally depends heavily on soybean meal as its primary protein source, an approach that leads to low nitrogen utilization and exacerbates environmental pollution from nitrogen emissions. Aspartate-family amino acids, including L-lysine, L-methionine, L-threonine, and L-isoleucine, represent the most significant category of feed amino acids, accounting for nearly 90% of global consumption. They address current challenges by balancing feed nutrition according to the ideal protein standard and enabling a low-carbon transition in animal husbandry. The primary production method for these four amino acids is microbial fermentation, predominantly using Escherichia coli and Corynebacterium glutamicum as host organisms. Rapid advances in systems biology, synthetic biology, metabolic engineering, and evolutionary engineering have facilitated the construction and optimization of high-yield amino acid-producing strains. This has significantly enhanced production efficiency and substantially reduced costs. Based on an analysis of the aspartate-family amino acid biosynthetic pathways, this paper details strain modification methods and strategies. These encompass four key aspects: metabolic pathway reconstruction, metabolic pathway optimization, cofactor supply enhancement, and improved product efflux. These approaches have enabled the industrial-scale production of strains achieving high titers and yields. Finally, future research directions are discussed, focusing on three fronts: enhancing strain stress resistance in industrial environments, expanding the range of utilizable substrates, and optimizing dynamic regulatory systems. These advancements aim to provide theoretical guidance and technical support for developing high-performance amino acid-producing strains. The ultimate goal is to support the global transition towards efficient and environmentally sustainable feed amino acid production, thereby alleviating pressures on protein resources.

Key words: aspartate-family amino acids, microbial cell factory, metabolic engineering, synthetic biology, gene editing

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