Regulation of Metabolic Flux at the Pyruvate-acetyl-CoA Node in Microalgae and Strategies for Enhancing High-value Product Synthesis

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

Abstract

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

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.

Figures/Tables 2

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

Fig. 2 Integrated application of various metabolic regulation strategies

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