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1.中国科学院深圳先进技术研究院,定量合成生物学全国重点实验室,深圳合成生物学创新研究院,广东 深圳 518055
2.中国科学院大学,北京 100049
Received:02 December 2024,
Revised:2025-02-20,
Published:30 June 2025
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李永珠, 陈禹. 酵母基因组规模模型进展及发展趋势[J]. 合成生物学, 2025, 6(3): 585-602
LI Yongzhu, CHEN Yu. Advances and prospects in genome-scale models of yeast[J]. Synthetic Biology Journal, 2025, 6(3): 585-602
李永珠, 陈禹. 酵母基因组规模模型进展及发展趋势[J]. 合成生物学, 2025, 6(3): 585-602 DOI: 10.12211/2096-8280.2024-084.
LI Yongzhu, CHEN Yu. Advances and prospects in genome-scale models of yeast[J]. Synthetic Biology Journal, 2025, 6(3): 585-602 DOI: 10.12211/2096-8280.2024-084.
酵母作为常用的真核模式生物,在合成生物学和系统生物学研究中具有重要地位。然而,由于其代谢系统较为复杂,进行代谢网络研究和设计时存在一定困难,因此,研究人员提出了基因组规模的建模方法,利用基因组序列及注释信息,整合细胞内复杂的代谢反应和细胞过程,模拟细胞系统各部分的相互作用,得到对应的表型、功能和行为,辅助寻找代谢工程改造靶点,为理解复杂细胞系统提供了强有力的工具。本文介绍了基因组规模模型中传统代谢模型及整合多种生理学约束和多种细胞过程的模型的构建和分析方法,回顾了酵母属中多种酵母基因组规模模型的发展历程及主要应用,并基于此分析了当前酵母基因组规模模型研究中面临的主要问题,提出了提升模型准确率以及未来进一步优化模型的方法和趋势。
Yeasts
particularly
Saccharomyces cerevisiae
are widely used eukaryotic organisms with relatively clear cellular structures and metabolic networks
and their cellular processes exhibit a certain degree of conservation among eukaryotes. These organisms play a crucial role in research with synthetic biology and systems biology as well. However
due to the complexity of their metabolic networks and the variability of cellular activities
study and design of pathways for yeasts still present considerable challenges. To address these issues
researchers have developed genome-scale models
which are mathematical framework that integrates genomic
biochemical
and physiological data to simulate cellular processes and predict the relationship between genotype and phenotype
which are further used to simulate cellular functions and predict cell behaviors under different conditions
providing a systematic approach for understanding and engineering biological systems. This review introduces methods for building and analyzing genome-scale models of yeasts
including traditional metabolic models and their derived multi-constraint and multi-process models. It also traces the development of yeast models over time. Furthermore
this article discusses recent applications of yeast models in areas such as designing yeasts as cell factories for producing valuable compounds
studying microbial physiology
optimizing cultivation conditions
and simulating microbial community interactions. These models also provide insights into identifying potential metabolic engineering targets for optimizing cellular functions. Despite the advantages of the genome-scale models
their develo
pment and application are still limited in several aspects
such as incomplete data on metabolic pathways
limited focus on secondary metabolism
and high barriers to use
particularly for users without programming backgrounds. This review proposes several strategies to address these challenges. To enhance the development of traditional models
it is crucial to incorporate more comprehensive datasets
with a particular emphasis on secondary metabolism and metabolic dark matters. Additionally
improving the accessibility of models requires the development of user-friendly platforms
the provision of clear and standardized tutorials. These strategies can lower barriers for users
and promote applications of the genome-scale models.
2
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