酵母合成芳香族氨基酸及其衍生物的代谢途径调控策略研究进展

doi:10.19586/j.2095-2341.2026.0076

生物技术进展 ›› 2026, Vol. 16 ›› Issue (3): 549-561.DOI: 10.19586/j.2095-2341.2026.0076

酵母合成芳香族氨基酸及其衍生物的代谢途径调控策略研究进展

刘英杰(), 马营, 栗宜德, 孔冬晴, 刘汉宇

齐鲁理工学院生物与化学工程学院，济南 250200

收稿日期:2026-03-24 接受日期:2026-04-17 出版日期:2026-05-25 发布日期:2026-07-14
作者简介:刘英杰 E-mail: liuyingjiezm@163.com
基金资助:
齐鲁理工学院科研计划项目(QIT24TP038)

Metabolic Regulation Strategies for Aromatic Amino Acids and Derivatives in Yeast: A Review

Yingjie LIU(), Ying MA, Yide LI, Dongqing KONG, Hanyu LIU

College of Biological and Chemical Engineering，Qilu Institute of Technology，Jinan 250200，China

Received:2026-03-24 Accepted:2026-04-17 Online:2026-05-25 Published:2026-07-14

摘要/Abstract

摘要：

芳香族氨基酸（aromatic amino acid, AAA）及其衍生物具有丰富的生物学功能，广泛应用于食品、医药等众多领域。随着合成生物学的发展，利用酵母进行微生物合成已成为绿色制造的研究热点。然而，酵母合成体系面临着代谢途径通量失衡、调控精度不足、底盘适配性差等问题，制约了大规模的生产应用。综述了酵母细胞工厂合成AAA及其衍生物的代谢路径调控策略。首先梳理了AAA的核心合成路径和主要限速瓶颈；继而从静态调控、时空动态调控、系统理性指导及人工智能等多个维度，归纳了代谢途径调控手段的演进；进一步分析了模式底盘（酿酒酵母）与非常规酵母在合成方面的代谢特性；最后总结了当前挑战并展望了未来方向，以期为构建高产酵母工程菌株提供策略参考。

关键词: 芳香族氨基酸, 酵母, 细胞工厂, 代谢途径调控

Abstract:

Aromatic amino acids （AAA） and their derivatives possess diverse biological functions and are widely applied in food， pharmaceutical， and other industrial sectors. With advances in synthetic biology， microbial synthesis using yeast has emerged as a research hotspot in green manufacturing. However， yeast-based production systems still face problems limiting large-scale application， including imbalanced metabolic flux， insufficient regulatory precision， and poor chassis adaptability. This review summarized recent advances in metabolic regulation strategies for the synthesis of AAA and their derivatives in yeast cell factories. Firstly， it outlined the core synthetic pathways and main rate-limiting bottlenecks of AAA； then， it summarized the evolution of metabolic pathway regulation methods from multiple dimensions such as static regulation， spatiotemporal dynamic regulation， systematic rational guidance， and artificial intelligence （AI）； further， it analyzed the metabolic characteristics of model chassis （Saccharomyces cerevisiae） and unconventional yeasts in synthesis； finally， it summarized the current challenges and looked forward to future directions， with the aim of providing strategic references for the construction of high-yield yeast engineering strains.

Key words: aromatic amino acids, yeast, cell factory, metabolic pathway regulation

中图分类号:

Q591.7

刘英杰, 马营, 栗宜德, 孔冬晴, 刘汉宇. 酵母合成芳香族氨基酸及其衍生物的代谢途径调控策略研究进展[J]. 生物技术进展, 2026, 16(3): 549-561.

Yingjie LIU, Ying MA, Yide LI, Dongqing KONG, Hanyu LIU. Metabolic Regulation Strategies for Aromatic Amino Acids and Derivatives in Yeast: A Review[J]. Current Biotechnology, 2026, 16(3): 549-561.

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链接本文: https://swjsjz.magtechjournal.com/CN/10.19586/j.2095-2341.2026.0076

https://swjsjz.magtechjournal.com/CN/Y2026/V16/I3/549

图/表 5

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底盘细胞	核心代谢特性	遗传操作便利性	合成芳香族化合物的优势	应用案例	主要局限
酿酒酵母	Crabtree阳性；中心碳代谢背景清晰；发酵能力强，尤其乙醇发酵；环境适应能力强^{[39, 68]}	遗传背景最清晰；基因操作工具最成熟^[75-78]	GRAS认证；调控机制清晰；天然具备合成某些衍生物（如酪醇）的能力^{[39, 65]}	种类繁多，如苯乙醇、香草醛、酪醇、红景天苷、莽草酸、对香豆酸、咖啡酸、柚皮素、山柰酚、褪黑素等^{[24, 26, 39, 75-77]}	前体供应不足；关键酶反馈抑制严格；对某些产物耐受性差^[65]
解脂耶氏酵母	Crabtree阴性；脂质积累/降解能力强；胞质乙酰辅酶A和丙二酰辅酶A丰富；底物谱广泛；环境适应能力独特（耐高渗且严格好氧）^[79]	遗传背景逐步明晰；基因操作工具部分建立（如CRISPR系统）^[79]	GRAS认证；乙酰辅酶A和丙二酰辅酶A供应充足，适合聚酮类/黄酮类合成；对某些产物耐受性强^[80-81]	种类繁多，如柚皮素、圣草酚、花旗松素、白藜芦醇、虎杖苷、对香豆酸、灯盏乙素等^{[38, 80]}	遗传工具库相对较少；菌丝形态转换影响工业化发酵^[36]
巴斯德毕赤酵母	Crabtree阴性；甲醇代谢独特；可分泌高效蛋白；环境适应能力独特（耐受低氧及高渗环境）^[82-84]	遗传背景逐步清晰；基因操作工具部分建立（如CRISPR系统及诱导系统）^[85]	GRAS认证；真核蛋白表达能力强（尤其适合复杂的P450酶）^[82-83]	相对较少，对香豆酸、柚皮素、白藜芦醇等^[82]	生长相对较慢；前体不足；通常不作为小分子化合物的首选生产底盘^[83-84]
马克斯克鲁维酵母	Crabtree阴性；中心碳代谢可塑性强；底物谱宽泛，擅长利用非常规碳源；环境适应能力独特（耐高温且生长快速）^{[11, 86]}	遗传背景日趋清晰；基因操作工具部分建立（如CRISPR、模块化表达载体）^[88]	GRAS认证；生长快；适合高温发酵节省成本，降低染菌风险；可利用部分廉价工业副产物^{[11, 86]}	相对较少，2-苯乙醇、乙醇酸等^[88]	遗传操作工具不够成熟；代谢认知不清晰^{[11, 86]}
其他非模式酵母	Crabtree效应复杂；中心碳代谢各异；底物谱广泛；环境适应能力可能耐受多重胁迫^{[12, 89]}	遗传背景有待进一步明晰；工具成熟度有待提升^[89]	某些酵母可利用廉价原料^[90]	可根据具体酵母特性进行研究，如对香豆酸、咖啡酸、阿魏酸、类胡萝卜素等^[89-90]	遗传背景待挖掘；遗传工具不足^[89]

底盘细胞	核心代谢特性	遗传操作便利性	合成芳香族化合物的优势	应用案例	主要局限
酿酒酵母	Crabtree阳性；中心碳代谢背景清晰；发酵能力强，尤其乙醇发酵；环境适应能力强^{[39, 68]}	遗传背景最清晰；基因操作工具最成熟^[75-78]	GRAS认证；调控机制清晰；天然具备合成某些衍生物（如酪醇）的能力^{[39, 65]}	种类繁多，如苯乙醇、香草醛、酪醇、红景天苷、莽草酸、对香豆酸、咖啡酸、柚皮素、山柰酚、褪黑素等^{[24, 26, 39, 75-77]}	前体供应不足；关键酶反馈抑制严格；对某些产物耐受性差^[65]
解脂耶氏酵母	Crabtree阴性；脂质积累/降解能力强；胞质乙酰辅酶A和丙二酰辅酶A丰富；底物谱广泛；环境适应能力独特（耐高渗且严格好氧）^[79]	遗传背景逐步明晰；基因操作工具部分建立（如CRISPR系统）^[79]	GRAS认证；乙酰辅酶A和丙二酰辅酶A供应充足，适合聚酮类/黄酮类合成；对某些产物耐受性强^[80-81]	种类繁多，如柚皮素、圣草酚、花旗松素、白藜芦醇、虎杖苷、对香豆酸、灯盏乙素等^{[38, 80]}	遗传工具库相对较少；菌丝形态转换影响工业化发酵^[36]
巴斯德毕赤酵母	Crabtree阴性；甲醇代谢独特；可分泌高效蛋白；环境适应能力独特（耐受低氧及高渗环境）^[82-84]	遗传背景逐步清晰；基因操作工具部分建立（如CRISPR系统及诱导系统）^[85]	GRAS认证；真核蛋白表达能力强（尤其适合复杂的P450酶）^[82-83]	相对较少，对香豆酸、柚皮素、白藜芦醇等^[82]	生长相对较慢；前体不足；通常不作为小分子化合物的首选生产底盘^[83-84]
马克斯克鲁维酵母	Crabtree阴性；中心碳代谢可塑性强；底物谱宽泛，擅长利用非常规碳源；环境适应能力独特（耐高温且生长快速）^{[11, 86]}	遗传背景日趋清晰；基因操作工具部分建立（如CRISPR、模块化表达载体）^[88]	GRAS认证；生长快；适合高温发酵节省成本，降低染菌风险；可利用部分廉价工业副产物^{[11, 86]}	相对较少，2-苯乙醇、乙醇酸等^[88]	遗传操作工具不够成熟；代谢认知不清晰^{[11, 86]}
其他非模式酵母	Crabtree效应复杂；中心碳代谢各异；底物谱广泛；环境适应能力可能耐受多重胁迫^{[12, 89]}	遗传背景有待进一步明晰；工具成熟度有待提升^[89]	某些酵母可利用廉价原料^[90]	可根据具体酵母特性进行研究，如对香豆酸、咖啡酸、阿魏酸、类胡萝卜素等^[89-90]	遗传背景待挖掘；遗传工具不足^[89]

酵母合成芳香族氨基酸及其衍生物的代谢途径调控策略研究进展

Metabolic Regulation Strategies for Aromatic Amino Acids and Derivatives in Yeast: A Review

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