SYNERGISTIC EFFECTS OF TARGETED MULTI-ENZYME SYSTEMS IN BIORECOVERY OF SECONDARY METABOLITES: FROM MECHANISTIC INSIGHTS TO OPTIMIZATION

Authors

  • Pham Thi Bich Phuong Nha Trang Central University Preparatory School for Ethnic Minority Students, Nha Trang, Vietnam Author
  • Bui Xuan Dong University of Science and Technology - The University of Da Nang image/svg+xml Author
  • Dang Xuan Cuong Ho Chi Minh City University of Industry and Trade image/svg+xml Author
  • Dang Thị Thanh Tuyen University of Science and Technology: Hanoi, Hanoi, VN Author
  • Nguyen Duy Linh Department of Science and Technology of Lam Dong Province, Lam Dong, Vietnam , Industrial University of Ho Chi Minh City image/svg+xml Author

DOI:

https://doi.org/10.60087/jklst.vol5.n2.002

Keywords:

Enzyme-assisted extraction, Targeted multi-enzyme systems, Enzyme synergism, Secondary metabolites, Process optimization

Abstract

The efficient recovery of plant-derived secondary metabolites has become a major research priority in response to the growing demand for sustainable production of high-value functional ingredients within the circular bioeconomy. Enzyme-assisted extraction (EAE) has emerged as a promising green extraction technology because of its high substrate specificity, mild operating conditions, and ability to preserve thermolabile bioactive compounds. However, the heterogeneous architecture of plant cell walls often limits the effectiveness of individual enzymes, emphasizing the need for rationally designed targeted multi-enzyme systems. This review provides a comprehensive and mechanism-oriented overview of recent advances in targeted multi-enzyme-assisted extraction for the recovery of plant secondary metabolites. Particular attention is given to plant cell wall architecture, molecular mechanisms of enzyme synergism, sequential deconstruction of pectin, hemicellulose, and cellulose, and the release mechanisms of matrix-bound bioactive compounds. The review further discusses rational strategies for designing biomass-specific enzyme cocktails based on substrate composition, enzyme complementarity, catalytic compatibility, and hydrolysis strategies. Recent developments in response surface methodology, kinetic modeling, artificial intelligence, and machine learning are critically evaluated as advanced tools for predictive process optimization. Emerging technologies, including multi-enzyme co-immobilization, protein engineering, synthetic biology, continuous bioprocessing, and integrated biorefinery concepts, are also reviewed with respect to their potential for improving catalyst utilization, process scalability, and industrial sustainability. Overall, this review demonstrates the transition of enzyme-assisted extraction from empirical optimization toward knowledge-driven, precision-designed bioprocesses integrating molecular enzymology, process engineering, and computational intelligence, providing a scientific framework for sustainable biomass valorization and next-generation circular biorefineries.

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References

[1] C. B. Penha, H. G. Falcão, E. I. Ida, P. Speranza, and L. E. Kurozawa, “Enzymatic pretreatment in the extraction process of soybean to improve protein and isoflavone recovery and to favor aglycone formation,” Food Research International, vol. 137, pp. 109624, 2020. doi: 10.1016/j.foodres.2020.109624.

[2] G. N. Ricarte, M. A. Z. Coelho, I. M. Marrucho, and B. D. Ribeiro, “Enzyme-assisted extraction of carotenoids and phenolic compounds from sunflower wastes using green solvents,” 3 Biotech, vol. 10, no. 9, 2020. doi: 10.1007/s13205-020-02393-0.

[3] A. Ali Redha, “Review on Extraction of Phenolic Compounds from Natural Sources Using Green Deep Eutectic Solvents,” Journal of Agricultural and Food Chemistry, vol. 69, no. 3, pp. 878-912, 2021. doi: 10.1021/acs.jafc.0c06641.

[4] S. J. Longhi, M. C. Martín, M. G. Merín, and V. I. Morata de Ambrosini, “Yeast Multi-Enzymatic Systems for Improving Colour Extraction, Technological Parameters and Antioxidant Activity of Wine,” Food Technology and Biotechnology, vol. 60, no. 4, pp. 556-570, 2022. doi: 10.17113/ftb.60.04.22.7777.

[5] Z. Lemoni, G. Theodoreli, S. Kalantzi, T. Lymperopoulou, A. Tzani, G. Stavropoulos, et al., “Process optimization and predictive modeling of multi-enzyme extraction of bioactive compounds from Rosa canina L,” Biotechnology for the Environment, vol. 3, no. 1, 2026. doi: 10.1186/s44314-026-00039-8.

[6] G. Domínguez-Rodríguez, M. C. García, M. L. Marina, and M. Plaza, “Pressurized Liquid Extraction Combined with Enzymatic-Assisted Extraction to Obtain Bioactive Non-Extractable Polyphenols from Sweet Cherry (Prunus avium L.) Pomace,” Nutrients, vol. 13, no. 9, pp. 3242, 2021. doi: 10.3390/nu13093242.

[7] M. José Aliaño González, C. Carrera, G. F. Barbero, and M. Palma, “A comparison study between ultrasound–assisted and enzyme–assisted extraction of anthocyanins from blackcurrant (Ribes nigrum L.),” Food Chemistry: X, vol. 13, pp. 100192, 2022. doi: 10.1016/j.fochx.2021.100192.

[8] O. R. Alara, N. H. Abdurahman, and C. I. Ukaegbu, “Extraction of phenolic compounds: A review,” Current Research in Food Science, vol. 4, pp. 200-214, 2021. doi: 10.1016/j.crfs.2021.03.011.

[9] N. Saad, F. Louvet, S. Tarrade, E. Meudec, K. Grenier, C. Landolt, et al., “Enzyme‐Assisted Extraction of Bioactive Compounds from Raspberry ( Rubus idaeus L.) Pomace,” Journal of Food Science, vol. 84, no. 6, pp. 1371-1381, 2019. doi: 10.1111/1750-3841.14625.

[10] A. P. Ghandahari Yazdi, M. Barzegar, M. A. Sahari, and H. Ahmadi Gavlighi, “Optimization of the enzyme‐assisted aqueous extraction of phenolic compounds from pistachio green hull,” Food Science & Nutrition, vol. 7, no. 1, pp. 356-366, 2018. doi: 10.1002/fsn3.900.

[11] M. R. Meini, I. Cabezudo, C. E. Boschetti, and D. Romanini, “Recovery of phenolic antioxidants from Syrah grape pomace through the optimization of an enzymatic extraction process,” Food Chemistry, vol. 283, pp. 257-264, 2019. doi: 10.1016/j.foodchem.2019.01.037.

[12] S. Das, S. S. Nadar, and V. K. Rathod, “Integrated strategies for enzyme assisted extraction of bioactive molecules: A review,” International Journal of Biological Macromolecules, vol. 191, pp. 899-917, 2021. doi: 10.1016/j.ijbiomac.2021.09.060.

[13] G. A. Macedo, Á. L. Santana, L. M. Crawford, S. C. Wang, F. F. Dias, and J. M. de Moura Bell, “Integrated microwave- and enzyme-assisted extraction of phenolic compounds from olive pomace,” LWT, vol. 138, pp. 110621, 2021. doi: 10.1016/j.lwt.2020.110621.

[14] A. Łubek-Nguyen, W. Ziemichód, and M. Olech, “Application of Enzyme-Assisted Extraction for the Recovery of Natural Bioactive Compounds for Nutraceutical and Pharmaceutical Applications,” Applied Sciences, vol. 12, no. 7, pp. 3232, 2022. doi: 10.3390/app12073232.

[15] D. Granato, M. Fidelis, M. Haapakoski, A. dos Santos Lima, J. Viil, J. Hellström, et al., “Enzyme-assisted extraction of anthocyanins and other phenolic compounds from blackcurrant (Ribes nigrum L.) press cake: From processing to bioactivities,” Food Chemistry, vol. 391, pp. 133240, 2022. doi: 10.1016/j.foodchem.2022.133240.

[16] H. C. Nguyen, K. N. Ngo, H. K. Tran, and C. J. Barrow, “Enzyme-Assisted Coextraction of Phenolics and Polysaccharides from Padina gymnospora,” Marine Drugs, vol. 22, no. 1, pp. 42, 2024. doi: 10.3390/md22010042.

[17] D. T. Y. Oanh, L. T. M. Hien, N. K. Duyen, N. H. Hieu, and D. T. A. Dao, “Effect of enzyme – assisted extraction on total polyphenol content and antioxidant capacity from fresh tea leaves (Camellia sinensis),” Vietnam Journal of Chemistry, vol. 61, no. 5, pp. 551-562, 2023. doi: 10.1002/vjch.202300109.

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Published

25-06-2026

How to Cite

Pham, P., Bui Xuan, D., Dang Xuan, C., Dang Thi Thanh, T., & Nguyen Duy, L. (2026). SYNERGISTIC EFFECTS OF TARGETED MULTI-ENZYME SYSTEMS IN BIORECOVERY OF SECONDARY METABOLITES: FROM MECHANISTIC INSIGHTS TO OPTIMIZATION. Journal of Knowledge Learning and Science Technology ISSN: 2959-6386 (online), 5(2), 26–47. https://doi.org/10.60087/jklst.vol5.n2.002

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