微藻丙酮酸-乙酰辅酶A节点代谢流调控与高值产物合成强化策略

doi:10.13560/j.cnki.biotech.bull.1985.2025-1141

摘要/Abstract

摘要：

微藻能固定二氧化碳、快速繁殖且合成多种高附加值产物，常作为优选的绿色细胞工厂。通过藻种改良和工艺改进提高其生产效率的相关研究备受关注。尽管大量研究提出并实践了有效的策略，但综合的应用方案仍有待进一步优化以满足微藻细胞工厂的规模化应用。基于微藻细胞的碳代谢通路，本文聚焦核心枢纽物质丙酮酸和乙酰辅酶A，沿节点上下游分析了高附加值产物合成途径中的关键限速酶及其编码基因。同时，系统讨论了提升高附加值产物生产效率的调控策略及相应的信号机制和代谢网络，这些策略主要涵盖：在宏观培养体系中优化光照参数、二氧化碳浓度、碳源类型、辅助性外源添加物、胁迫强度和藻菌互作；以及在藻种层面开展诱变育种、基因工程和表观修饰等遗传改良。通过策略优选和组合能使微藻生长、应激和产物积累的平衡达到最优解，实现增加前体供应，定向强化目标产物合成的目的。此外，在人工智能技术的驱动下，微藻高附加值产物的合成能力有望在多个维度上获得系统性增强，包括识别限速步骤、预测基因编辑靶点、重塑代谢流；同时实现培养体系重要参数的实时监测、动态调控、数据库构建和迭代改进。依托智能化技术驱动多维度策略融合，将进一步推动基于微藻细胞工厂的绿色生物制造。

关键词: 微藻细胞工厂, 高附加值产物, 碳代谢流, 分子机制, 调控策略

Abstract:

Microalgae are recognized for their ability to fix carbon dioxide, proliferate rapidly, and synthesize a wide range of high-value-added products, making them preferred green cell factories. Considerable attention is focused on enhancing productivity through strain improvement and process optimization. However, although numerous effective strategies have been proposed and implemented, the development and application of integrated approaches remain insufficient to meet the demands of large-scale microalgae-based manufacturing. Based on microalgal carbon metabolism pathways, this review focuses on two core metabolic hubs: pyruvate, acetyl-CoA and examines key rate-limiting enzymes and encoding genes in the upstream and downstream pathways for synthesizing high-value-added products. Meanwhile, it systematically discusses regulatory strategies for improving the production efficiency of high value-added products, along with the corresponding signaling mechanisms and metabolic networks. These strategies primarily encompass optimizing light conditions, carbon dioxide concentration, carbon source types, supplementary exogenous additives, stress intensity, and algal-bacterial interactions within the macro-level cultivation system; as well as implementing genetic improvements such as mutagenesis breeding, genetic engineering, and epigenetic modifications at the strain level. These strategies aim to achieve an optimal balance among microalgal growth, stress response, and product accumulation, thereby enhancing precursor supply and directing metabolic flux toward target product synthesis. Furthermore, driven by artificial intelligence technology, the synthetic capability of high-value-added microalgae products is expected to achieve systematic enhancement across multiple dimensions, including identification of rate-limiting steps, prediction of gene-editing targets, and remodeling of metabolic flows. Concurrently, it aims to achieve real-time monitoring of key parameters in the cultivation system, dynamic regulation, database construction, and iterative improvement. Driven by intelligent technologies and relying on the integration of multi-dimensional strategies, it is expected to further advance green biomanufacturing based on microalgal cell factories.

Key words: microalgae cell factories, high-value-added products, carbon flux, molecular mechanism, regulation strategy

张书翰, 任海伟, 陆栋, 罗光宏, 王永刚, 郭晓鹏. 微藻丙酮酸-乙酰辅酶A节点代谢流调控与高值产物合成强化策略[J]. 生物技术通报, 2026, 42(7): 34-47.

ZHANG Shu-han, REN Hai-wei, LU Dong, LUO Guang-hong, WANG Yong-gang, GUO Xiao-peng. Regulation of Metabolic Flux at the Pyruvate-acetyl-CoA Node in Microalgae and Strategies for Enhancing High-value Product Synthesis[J]. Biotechnology Bulletin, 2026, 42(7): 34-47.

图/表 2

图1 微藻合成高附加值产物的代谢途径HK：己糖激酶；PKF-1：磷酸果糖激酶-1；PK：丙酮酸激酶；PDC：丙酮酸脱氢酶复合体；ACCase：乙酰辅酶A羧化酶；FAS：脂肪酸合酶复合体；G3P：甘油醛-3-磷酸；DXS：1-脱氧-D-木酮糖-5-磷酸合酶；DXP：1-脱氧-D-木酮糖-5-磷酸；DXR：1-脱氧-D-木酮糖-5-磷酸还原异构酶；MEP：2-甲基-D-赤藓醇-4-磷酸；MEcPP：2-甲基-D-赤藓醇-2,4-环焦磷酸；HDS：4-羟基-3-甲基-2-丁烯基焦磷酸合酶；HMBPP：4-羟基-3-甲基-2-丁烯基焦磷酸；HDR：4-羟基-3-甲基-2-丁烯基焦磷酸还原酶；IPP：异戊烯基焦磷酸；DMAPP：二甲基烯丙基焦磷酸；IDI：异戊烯基焦磷酸异构酶；GGPPS：牻牛儿基牻牛儿基焦磷酸合酶；GGPP：牻牛儿基牻牛儿基焦磷酸；PSY：八氢番茄红素合酶；PDS：八氢番茄红素去饱和酶；ZDS：ζ-胡萝卜素去饱和酶；LCYE：番茄红素ε-环化酶；LCYB：番茄红素β-环化酶；CYP97：细胞色素P450型羟化酶；CrtR：β-胡萝卜素羟化酶；BKT：β-胡萝卜素酮化酶；CS：柠檬酸合酶；AACT：乙酰乙酰辅酶A硫解酶；HMGS：3-羟基-3-甲基戊二酰辅酶A合酶；HMG-CoA：3-羟基-3-甲基戊二酰辅酶A；HMGR：3-羟基-3-甲基戊二酰辅酶A还原酶；MVK：甲羟戊酸激酶；PMK：磷酸甲羟戊酸激酶；MVD：二磷酸甲羟戊酸脱羧酶；MVA：甲羟戊酸；MVAP：5-磷酸甲羟戊酸；MVAPP：5-二磷酸甲羟戊酸

Fig. 1 Metabolic pathways for the synthesis of high-value-added products in microalgaeHK: Hexokinase; PFK-1: phosphofructokinase-1; PK: pyruvate kinase; PDC: pyruvate dehydrogenase complex; ACCase: acetyl-CoA carboxylase; FAS: fatty acid synthase complex; G3P: glyceraldehyde-3-phosphate; DXS: 1-deoxy-D-xylulose-5-phosphate synthase; DXP: 1-deoxy-D-xylulose-5-phosphate; DXR: 1-deoxy-D-xylulose-5-phosphate reductoisomerase; MEP: 2-C-methyl-D-erythritol-4-phosphate; MEcPP: 2-C-methyl-D-erythritol-2,4-cyclodiphosphate; HDS: 4-hydroxy-3-methylbut-2-enyl diphosphate synthase; HMBPP: 4-hydroxy-3-methylbut-2-enyl diphosphate; HDR: 4-hydroxy-3-methylbut-2-enyl diphosphate reductase; IPP: isopentenyl diphosphate; DMAPP: dimethylallyl diphosphate; IDI: isopentenyl diphosphate isomerase; GGPPS: geranylgeranyl diphosphate synthase; GGPP: geranylgeranyl diphosphate; PSY: phytoene synthase; PDS: phytoene desaturase; ZDS: ζ-carotene desaturase; LCYE: lycopene ε-cyclase; LCYB: lycopene β-cyclase; CYP97: cytochrome P450-type hydroxylase; CrtR: β-carotene hydroxylase; BKT: β-carotene ketolase; CS: citrate synthase; AACT: acetoacetyl-CoA thiolase; HMGS: 3-hydroxy-3-methylglutaryl-CoA synthase; HMG-CoA: 3-hydroxy-3-methylglutaryl-CoA; HMGR: 3-hydroxy-3-methylglutaryl-CoA reductase; MVK: mevalonate kinase; PMK: phosphomevalonate kinase; MVD: mevalonate diphosphate decarboxylase; MVA: mevalonic acid; MVAP: mevalonate-5-phosphate; MVAPP: mevalonate-5-diphosphate

图2 多种代谢调控策略的综合应用

Fig. 2 Integrated application of various metabolic regulation strategies

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