Metabolic Engineering Strategies and Application Advances of Microbial Cell Factories for Carotenoid Production

doi:10.19586/j.2095-2341.2026.0065

Current Biotechnology ›› 2026, Vol. 16 ›› Issue (3): 523-534.DOI: 10.19586/j.2095-2341.2026.0065

• Special Forum on Microbial Cell Factory • Previous Articles Next Articles

Metabolic Engineering Strategies and Application Advances of Microbial Cell Factories for Carotenoid Production

Juan LI(), Yuting HE(), Xiaoxuan YE(), Jiayi JIA(), Yaohui ZHANG, Hongyang ZHANG(), Tao WU()

College of Biotechnology and Food Science，Tianjin University of Commerce，Tianjin 300134，China

Received:2026-03-16 Accepted:2026-04-20 Online:2026-05-25 Published:2026-07-14
Contact: Hongyang ZHANG,Tao WU

Abstract

Abstract:

Carotenoids represent an important class of terpenoid natural pigments with wide applications in food， pharmaceutical， and cosmetic industries. Benefiting from rapid growth， facile genetic manipulation， and scalable cultivation， microbial cell factories have emerged as a promising platform for carotenoid production. This paper systematically summarized metabolic engineering strategies applied in carotenoid biosynthesis in prokaryotic microorganisms typified by Escherichia coli and eukaryotic microorganisms represented by Saccharomyces cerevisiae and Yarrowia lipolytica. Major advances were highlighted， including optimization of precursor supply pathways， engineering of key enzymes， redirection of metabolic flux， regulation of cofactors， membrane engineering， and the combined application of multiple strategies. On this basis， the article compared the differences in membrane systems between prokaryotes and eukaryotes and discussed their implications for membrane engineering strategies. The unique advantages of the oleaginous yeast Yarrowia lipolytica for carotenoid synthesis and its adaptive laboratory evolution strategies were also addressed. Finally， prospects for artificial intelligence （AI）-assisted optimization of metabolic elements and other future research directions were presented， with the aim of providing references for the green and efficient biomanufacturing and industrial application of carotenoids.

Key words: carotenoids, microbial cell factories, metabolic engineering, membrane engineering, Yarrowia lipolytica, artificial intelligence

CLC Number:

Q291

Juan LI, Yuting HE, Xiaoxuan YE, Jiayi JIA, Yaohui ZHANG, Hongyang ZHANG, Tao WU. Metabolic Engineering Strategies and Application Advances of Microbial Cell Factories for Carotenoid Production[J]. Current Biotechnology, 2026, 16(3): 523-534.

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Figures/Tables 5

References 61

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代表物种	代谢工程改造策略	核心产量	培养方式	参考文献
大肠杆菌	过表达MEP途径dxs+ispG基因，强化IPP/DMAPP前体合成	IPP/DMAPP产量提升1.8倍，β-胡萝卜素从120 mg·L^-1增至216 mg·L^-1	摇瓶	[11]
	导入异源MVA途径	β-胡萝卜素产量达465 mg·L^-1，前体IPP供应提升2.3倍	发酵罐	[11]
	改造MEP模块、β-胡萝卜素合成核心模块	MEP模块的工程使β-胡萝卜素产量提高3.5倍，而β-胡萝卜素合成模块的工程则使产量提高3.4倍	补料分批发酵	[14]
	优化MEP和MVA途径	β-胡萝卜素产量达3.2 g·L^-1，甘油转化为β-胡萝卜素（克对克）的转化效率达到2.76%	5 L发酵罐	[12]
	平衡强化MEP途径中IspG和IspH，消除中间产物积累	β-胡萝卜素和番茄红素滴度分别增加73%和77%	摇瓶	[16]
	多基因组合组装	番茄红素滴度提升3倍，最高可达448 mg·g^-1DCW	摇瓶	[21]
	crtE定点突变（A110V），提升GGPP合成酶催化效率	在M9最小培养基中积累了16 mg·g^-1 DCW的茄红素	摇瓶	[25]
	基于RBS序列调节dxs、idi和crt基因簇的转录水平	β-胡萝卜素产量提高8倍，最终产量达17.59 mg·g^-1 DCW	摇瓶/微型发酵罐	[27]
	敲除yjgB（消耗NADPH），过表达nadK（将NADH转化为NADPH）；敲除zgf，用galP替代ptsHIcrr葡萄糖转运系统	β-胡萝卜素产量达2.58 g·L^-1	5 L发酵罐	[33]
	激活atoB基因，利用退化RBS库对关键酶Mvas和Hmg1进行研究	β-胡萝卜素含量提升了51%	摇瓶	[35]
	改造甘油利用途径，优化非粮碳源利用	甘油培养基中类胡萝卜素产量较天然提取提升86%	摇瓶	[36]
	构建葡萄糖-木糖协同利用系统，实现碳源分工代谢	α-胡萝卜素产量达1 802 mg·L^-1	摇瓶	[37]
	优化基因配置、融合标签、发酵条件、FVSEOF靶点过表达、hok/sok质粒稳定系统及降低异丙基-β-D-硫代半乳糖苷（isopropyl β-D-1-thiogalactopyranoside，IPTG）代谢负荷等策略	虾红素最高产量432.82 mg·L^-1，7.12 mg·g^-1 DCW，产率达9.62 mg·L^-1·h^-1	5 L发酵罐	[40]
	利用CRISPR/Cas9技术精准敲除类胡萝卜素合成竞争途径基因	β-胡萝卜素达2.0 g·L^-1；构建15个靶点突变高产菌株	补料分批发酵	[46]
	过表达膜弯曲蛋白来工程化膜形态,优化设计膜合成途径	β-类胡萝卜素特异性产值提高2.9倍（从6.7 mg·g^-1 DCW提升至19.6 mg·g^-1 DCW）	摇瓶	[47]
谷氨酸棒状菌	开发CRISPR/Mad7系统实现多基因一步敲除，过表达sigA基因优化代谢流，RBS序列调控CrtW/CrtZ翻译起始速率	总类胡萝卜素发酵罐产量达1.45 g·L^-1	2 L发酵罐	[32]

代表物种	代谢工程改造策略	核心产量	培养方式	参考文献
大肠杆菌	过表达MEP途径dxs+ispG基因，强化IPP/DMAPP前体合成	IPP/DMAPP产量提升1.8倍，β-胡萝卜素从120 mg·L^-1增至216 mg·L^-1	摇瓶	[11]
	导入异源MVA途径	β-胡萝卜素产量达465 mg·L^-1，前体IPP供应提升2.3倍	发酵罐	[11]
	改造MEP模块、β-胡萝卜素合成核心模块	MEP模块的工程使β-胡萝卜素产量提高3.5倍，而β-胡萝卜素合成模块的工程则使产量提高3.4倍	补料分批发酵	[14]
	优化MEP和MVA途径	β-胡萝卜素产量达3.2 g·L^-1，甘油转化为β-胡萝卜素（克对克）的转化效率达到2.76%	5 L发酵罐	[12]
	平衡强化MEP途径中IspG和IspH，消除中间产物积累	β-胡萝卜素和番茄红素滴度分别增加73%和77%	摇瓶	[16]
	多基因组合组装	番茄红素滴度提升3倍，最高可达448 mg·g^-1DCW	摇瓶	[21]
	crtE定点突变（A110V），提升GGPP合成酶催化效率	在M9最小培养基中积累了16 mg·g^-1 DCW的茄红素	摇瓶	[25]
	基于RBS序列调节dxs、idi和crt基因簇的转录水平	β-胡萝卜素产量提高8倍，最终产量达17.59 mg·g^-1 DCW	摇瓶/微型发酵罐	[27]
	敲除yjgB（消耗NADPH），过表达nadK（将NADH转化为NADPH）；敲除zgf，用galP替代ptsHIcrr葡萄糖转运系统	β-胡萝卜素产量达2.58 g·L^-1	5 L发酵罐	[33]
	激活atoB基因，利用退化RBS库对关键酶Mvas和Hmg1进行研究	β-胡萝卜素含量提升了51%	摇瓶	[35]
	改造甘油利用途径，优化非粮碳源利用	甘油培养基中类胡萝卜素产量较天然提取提升86%	摇瓶	[36]
	构建葡萄糖-木糖协同利用系统，实现碳源分工代谢	α-胡萝卜素产量达1 802 mg·L^-1	摇瓶	[37]
	优化基因配置、融合标签、发酵条件、FVSEOF靶点过表达、hok/sok质粒稳定系统及降低异丙基-β-D-硫代半乳糖苷（isopropyl β-D-1-thiogalactopyranoside，IPTG）代谢负荷等策略	虾红素最高产量432.82 mg·L^-1，7.12 mg·g^-1 DCW，产率达9.62 mg·L^-1·h^-1	5 L发酵罐	[40]
	利用CRISPR/Cas9技术精准敲除类胡萝卜素合成竞争途径基因	β-胡萝卜素达2.0 g·L^-1；构建15个靶点突变高产菌株	补料分批发酵	[46]
	过表达膜弯曲蛋白来工程化膜形态,优化设计膜合成途径	β-类胡萝卜素特异性产值提高2.9倍（从6.7 mg·g^-1 DCW提升至19.6 mg·g^-1 DCW）	摇瓶	[47]
谷氨酸棒状菌	开发CRISPR/Mad7系统实现多基因一步敲除，过表达sigA基因优化代谢流，RBS序列调控CrtW/CrtZ翻译起始速率	总类胡萝卜素发酵罐产量达1.45 g·L^-1	2 L发酵罐	[32]

代表物种	代谢工程改造策略	核心产量	培养方式	参考文献
酿酒酵母	利用木糖代谢自带的呼吸型代谢特征、胞质乙酰CoA富集，以及ACS1、HMG1等限速基因天然上调表达	β-胡萝卜素产量达772.8 mg·L^-1	摇瓶	[18]
	构建无诱导/抑制子的动态控制策略，平衡利用酿酒酵母中相同前体的2种通路	类胡萝卜素产量达1 156 mg·L^-1	5 L发酵罐	[30]
	去中心化组装并通过重复使用双向启动子等方式	总类胡萝卜素产量达11 mg·g^-1 DCW，β-胡萝卜素产量达7.41 mg·g^-1 DCW	摇瓶	[23]
解脂耶氏酵母	MVA和类胡萝卜素途径模块化优化	虾青素产量达172.1 mg·L^-1	发酵罐	[19]
	进一步表达限速酶tHMGR及β-胡萝卜素合成相关基因的拷贝数	β-胡萝卜素产量达117.5 mg·L^-1	5 L发酵罐	[24]
	优化合成基因拷贝数，强化脂肪酸合成辅助产物储存	番茄红素产量达62 mg·g^-1 DCW	摇瓶	[28]
	路径基因启动子的组合适配（筛选每个转录单位的最佳启动子-基因对）并结合发酵条件优化	β-胡萝卜素产量达6.5 g·L^-1(90 mg·g^-1 DCW)	发酵罐	[42]
	过氧化物酶体靶向	玉米黄质的滴度达到412 mg·L^-1	发酵罐	[48]
	敲除脂代谢基因（POX2、MFE、POX3、LIP1）增强脂质积累；过表达HMGR，ERG13，增强MVA途径；增加crtYB、crtI、crtE拷贝数	β-胡萝卜素产量达4.5 g·L^-1	5 L发酵罐	[49]
胶红酵母	通过单因素和响应面法优化合成培养基（葡萄糖、蛋白胨、NaH₂PO₄·2H₂O）及培养条件	摇瓶中总类胡萝卜素浓度为103.02 mg·L^-1；5 L罐放大后达533.72 mg·L^-1	摇瓶；5 L发酵罐	[44]
毕赤酵母	通过系统优化类异戊二烯前体供给、脂质代谢与细胞储存能力，显著提升了番茄红素合成水平	补料分批发酵实现番茄红素7.24 g·L^-1的产量	发酵罐	[50]

代表物种	代谢工程改造策略	核心产量	培养方式	参考文献
酿酒酵母	利用木糖代谢自带的呼吸型代谢特征、胞质乙酰CoA富集，以及ACS1、HMG1等限速基因天然上调表达	β-胡萝卜素产量达772.8 mg·L^-1	摇瓶	[18]
	构建无诱导/抑制子的动态控制策略，平衡利用酿酒酵母中相同前体的2种通路	类胡萝卜素产量达1 156 mg·L^-1	5 L发酵罐	[30]
	去中心化组装并通过重复使用双向启动子等方式	总类胡萝卜素产量达11 mg·g^-1 DCW，β-胡萝卜素产量达7.41 mg·g^-1 DCW	摇瓶	[23]
解脂耶氏酵母	MVA和类胡萝卜素途径模块化优化	虾青素产量达172.1 mg·L^-1	发酵罐	[19]
	进一步表达限速酶tHMGR及β-胡萝卜素合成相关基因的拷贝数	β-胡萝卜素产量达117.5 mg·L^-1	5 L发酵罐	[24]
	优化合成基因拷贝数，强化脂肪酸合成辅助产物储存	番茄红素产量达62 mg·g^-1 DCW	摇瓶	[28]
	路径基因启动子的组合适配（筛选每个转录单位的最佳启动子-基因对）并结合发酵条件优化	β-胡萝卜素产量达6.5 g·L^-1(90 mg·g^-1 DCW)	发酵罐	[42]
	过氧化物酶体靶向	玉米黄质的滴度达到412 mg·L^-1	发酵罐	[48]
	敲除脂代谢基因（POX2、MFE、POX3、LIP1）增强脂质积累；过表达HMGR，ERG13，增强MVA途径；增加crtYB、crtI、crtE拷贝数	β-胡萝卜素产量达4.5 g·L^-1	5 L发酵罐	[49]
胶红酵母	通过单因素和响应面法优化合成培养基（葡萄糖、蛋白胨、NaH₂PO₄·2H₂O）及培养条件	摇瓶中总类胡萝卜素浓度为103.02 mg·L^-1；5 L罐放大后达533.72 mg·L^-1	摇瓶；5 L发酵罐	[44]
毕赤酵母	通过系统优化类异戊二烯前体供给、脂质代谢与细胞储存能力，显著提升了番茄红素合成水平	补料分批发酵实现番茄红素7.24 g·L^-1的产量	发酵罐	[50]

代表物种	代谢工程改造策略	核心产量	培养方式	参考文献
集胞藻PCC 6803	导入外源基因重构完整虾青素合成通路，实现虾青素的从头合成	氮饥饿14 d后，PCC6803突变株每克细胞(干重)合成4.81±0.06 mg虾青素	光合培养，胁迫诱导（氮饥饿处理14 d）	[54]
莱茵衣藻	共表达BKT、CrtB、ChyB，强化虾青素合成途径	混合营养虾青素达9.5 mg·L^-1，高密度培养达23.5 mg·L^-1（提升4倍）	发酵罐	[55]
雨生红球藻	pds定点突变与核稳定转化	强光48 h，P3 虾青素 11.4 mg·g^-1干重，增产26%	低光养菌，强光诱导合成	[56]

Metabolic Engineering Strategies and Application Advances of Microbial Cell Factories for Carotenoid Production

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