Rational screening and mechanistic elucidation of surfactants for mitigating phenolic inhibition in lignocellulose enzymatic hydrolysis: Combining experimental and computational approaches

Xiaoxiao Jiang; Zhanyu Wang; Yujie Wang; Lai Heng Tan; Xu Yang; Shuyi Jin; Yuguang Mu; Rui Zhai; Tao Wei; Mingjie Jin

doi:10.1016/j.jobab.2026.100250

Volume 11 Issue 2

May 2026

Turn off MathJax

Article Contents

Article Navigation > Journal of Bioresources and Bioproducts > 2026 > 11(2): 100250

Xiaoxiao Jiang, Zhanyu Wang, Yujie Wang, Lai Heng Tan, Xu Yang, Shuyi Jin, Yuguang Mu, Rui Zhai, Tao Wei, Mingjie Jin. Rational screening and mechanistic elucidation of surfactants for mitigating phenolic inhibition in lignocellulose enzymatic hydrolysis: Combining experimental and computational approaches[J]. Journal of Bioresources and Bioproducts, 2026, 11(2): 100250. doi: 10.1016/j.jobab.2026.100250

Citation:

Xiaoxiao Jiang, Zhanyu Wang, Yujie Wang, Lai Heng Tan, Xu Yang, Shuyi Jin, Yuguang Mu, Rui Zhai, Tao Wei, Mingjie Jin. Rational screening and mechanistic elucidation of surfactants for mitigating phenolic inhibition in lignocellulose enzymatic hydrolysis: Combining experimental and computational approaches[J]. Journal of Bioresources and Bioproducts, 2026, 11(2): 100250. doi: 10.1016/j.jobab.2026.100250

Citation:

Xiaoxiao Jiang, Zhanyu Wang, Yujie Wang, Lai Heng Tan, Xu Yang, Shuyi Jin, Yuguang Mu, Rui Zhai, Tao Wei, Mingjie Jin. Rational screening and mechanistic elucidation of surfactants for mitigating phenolic inhibition in lignocellulose enzymatic hydrolysis: Combining experimental and computational approaches[J]. Journal of Bioresources and Bioproducts, 2026, 11(2): 100250. doi: 10.1016/j.jobab.2026.100250

PDF( 2345 KB)

Rational screening and mechanistic elucidation of surfactants for mitigating phenolic inhibition in lignocellulose enzymatic hydrolysis: Combining experimental and computational approaches

doi: 10.1016/j.jobab.2026.100250

a College of Food and Bioengineering, Zhengzhou University of Light Industry, Zhengzhou 450001, China;
b Integrated Graduate Program, Nanyang Technological University, Singapore 639798, Singapore;
c School of Biological Sciences, Nanyang Technological University, Singapore 639798, Singapore;
d School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, China

Funds:

No. 262102310554).

This work was supported by China Postdoctoral Science Foundation (No. 2025M781138), Key Scientific Research Projects of Colleges and Universities in Henan Province (No. 25B416002), Doctoral Scientific Research Foundation of Zhengzhou University of Light Industry (No. 2024BSJJ025), Key Research and Development Projects in Henan Province (No. 241111110400), Key Projects of Science and Technology Development Joint Fund in Henan Province (No. 235200810023), and Key Research Projects of the Science and Technology Department of Henan Province (No. 262102320147

Received Date: 2025-12-17
Accepted Date: 2026-02-06
Rev Recd Date: 2026-01-30

Available Online: 2026-05-07

Publish Date: 2026-03-27

Abstract

Abstract

Lignin-derived phenolic compounds pose a critical bottleneck in the sustainable enzymatic hydrolysis of lignocellulose by causing severe enzyme inhibition. While surfactants can significantly alleviate this inhibition, their structure-function relationships and underlying molecular mechanisms remain unclear. In this study, the mitigating effects of various surfactants were quantitatively characterized, revealing that hydrophobicity, hydrogen bonding ability, and electrophilicity are the key structural descriptors for their efficacy. Experimental analysis confirmed that selected surfactants significantly mitigated phenolic-induced enzyme deactivation and precipitation. Circular dichroism spectroscopy further revealed that surfactants effectively restored the secondary structure (specifically α-helix content) and stabilized the enzyme conformation against phenolic denaturation. Molecular docking simulations demonstrated that surfactants preferentially bind within the catalytic tunnel of cellulase with stronger affinities (from -20.08 to -29.71 kJ/mol) compared to phenolics, driven by hydrogen bond anchoring reinforced by extensive hydrophobic and π-π stacking interactions with key tunnel residues. Collectively, these findings support a competitive stabilization mechanism, providing new insights into the surfactant-mediated protection of cellulase, facilitating more efficient lignocellulose enzymatic hydrolysis.
- Lignocellulose,
- Enzymatic hydrolysis,
- Surfactants,
- Phenolic inhibition,
- Mitigating effect,
- Quantitative structure-activity relationship (QSAR)

FullText(HTML)

References(45)

References

[1]	Adasme, M.F., Linnemann, K.L., Bolz, S.N., Kaiser, F., Salentin, S., Haupt, V.J., Schroeder, M., 2021. PLIP 2021: expanding the scope of the protein-ligand interaction profiler to DNA and RNA. Nucleic Acids Res. 49, W530–W534.
[2]	Agrawal, R., Satlewal, A., Kapoor, M., Mondal, S., Basu, B., 2017. Investigating the enzyme-lignin binding with surfactants for improved saccharification of pilot scale pretreated wheat straw. Bioresour. Technol. 224, 411–418.
[3]	Ahmed, E.M., Al-hasni, B., 2020. Dielectric properties, polarizability and molar refractive index of some VSrFeZnO glasses. J. Microw. Power Electromagn. Energy 54, 291–311.
[4]	Becher, P. 1984. Hydrophile-lipophile balance: history and recent developments (Langmuir lecture, 1983). J. Dispersion Sci. Technol. 5, 81–96.
[5]	Beltran-Perez, C., Serrano, A.A.A., Solís-Rosas, G., Martínez-Jiménez, A., Orozco-Cruz, R., Espinoza-Vázquez, A., Miralrio, A., 2022. A general use QSAR-ARX model to predict the corrosion inhibition efficiency of drugs in terms of quantum mechanical descriptors and experimental comparison for lidocaine. Int. J. Mol. Sci. 23, 5086.
[6]	Bradford, M., 1976. A rapid and sensitive for the quantitation of microgram quantitites of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1, 248–254.
[7]	Cai, C., Zhang, C.F., Li, N., Liu, H.F., Xie, J., Lou, H.M., Pan, X.J., Zhu, J.Y., Wang, F., 2023. Changing the role of lignin in enzymatic hydrolysis for a sustainable and efficient sugar platform. Renew. Sustain. Energy Rev. 183, 113445.
[8]	Chen, Z.H., Chen, L., Khoo, K.S., Gupta, V.K., Sharma, M., Show, P.L., Yap, P.S., 2023. Exploitation of lignocellulosic-based biomass biorefinery: a critical review of renewable bioresource, sustainability and economic views. Biotechnol. Adv. 69, 108265.
[9]	Dadfar, E., Shafiei, F., 2020. Prediction of some thermodynamic properties of sulfonamide drugs using genetic algorithm-multiple linear regressions. J. Chin. Chem. Soc. 67, 492–513.
[10]	Deng, Y.J., Wang, X., Zhang, C.H., Xie, P.J., Huang, L.X., 2023. Inhibitory effect of a Chinese quince seed peptide on protein glycation: a mechanism study. J. Bioresour. Bioprod. 8, 187–197.
[11]	Geng, A.L., Zou, G., Yan, X., Wang, Q.F., Zhang, J., Liu, F.H., Zhu, B.L., Zhou, Z.H., 2012. Expression and characterization of a novel metagenome-derived cellulase Exo2b and its application to improve cellulase activity in Trichoderma reesei. Appl. Microbiol. Biotechnol. 96, 951–962.
[12]	Hao, J.J., Chen, H.F., Zhang, C.Q., Li, H.L., Chen, X.F., Xiong, Z., Wang, C., Guo, H.J., Zhang, H.R., Xiong, L., Yu, S.S., Chen, X.D., 2025. Reducing lignin condensation and enhancing enzymatic hydrolysis of wheat straw by low-concentration p-toluenesulfonic acid pretreatment assisted with polyethylene glycol. Chem. Eng. J. 511, 162012.
[13]	Hu, J.W., Zhang, X.Y., Wang, Z.W., 2010. A review on progress in QSPR studies for surfactants. Int. J. Mol. Sci. 11, 1020–1047.
[14]	Huang, C.X., Jiang, X., Shen, X.J., Hu, J.G., Tang, W., Wu, X.X., Ragauskas, A., Jameel, H., Meng, X.Z., Yong, Q., 2022. Lignin-enzyme interaction: a roadblock for efficient enzymatic hydrolysis of lignocellulosics. Renew. Sustain. Energy Rev. 154, 111822.
[15]	Jiang, X.X., Wang, Y.J., Wang, Z.Y., Yang, X., Mu, Y.G., Zhai, R., Wei, T., Jin, M.J., 2026. Surfactants as process intensifiers in lignocellulosic sugar-platform biorefineries: mechanistic insights and bioprocess implications. Biotechnol. Adv. 88, 108837.
[16]	Jiang, X.X., Zhai, R., Leng, Y., Deng, Q.F., Jin, M.J., 2022. Understanding the toxicity of lignin-derived phenolics towards enzymatic saccharification of lignocellulose for rationally developing effective in-situ mitigation strategies to maximize sugar production from lignocellulosic biorefinery. Bioresour. Technol. 349, 126813.
[17]	Jiang, X.X., Zhai, R., Li, H.X., Li, C., Deng, Q.F., Wu, X.L., Jin, M.J., 2023. Binary additives for in-situ mitigating the inhibitory effect of lignin-derived phenolics on enzymatic hydrolysis of lignocellulose: enhanced performance and synergistic mechanism. Energy 282, 128062.
[18]	Joshi, V.Y., Kadam, M.M., Sawant, M.R., 2007. Comparison of QSAR and QSPR based aquatic toxicity for mixed surfactants. J. Surfactants Deterg. 10, 25–34.
[19]	Kiyooka, S.I., Kaneno, D., Fujiyama, R., 2013. Parr’s index to describe both electrophilicity and nucleophilicity. Tetrahedron Lett. 54, 339–342.
[20]	Lee, N.S., Shin, H.K., Kim, Y.J., Kim, C.H., Suh, S.H., 2010. HOMO-LUMO energy gap analysis of alkyl viologen with a positively charged aromatic ring. Revue Roumaine De Chimie 55, 627–632.
[21]	Liu, Q.Q., Madadi, M., Al Azad, S., Sun, C.H., Zhang, E.Z., Yan, J.S., Samimi, A., Sun, F.B., 2025a. In-depth recognition of mixed surfactants maintaining the enzymatic activity of cellulases through stabilization of their spatial structures. Bioresour. Technol. 416, 131756.
[22]	Liu, T., Wang, P.P., Tian, J., Guo, J.Q., Zhu, W.Y., Bushra, R., Huang, C.X., Jin, Y.C., Xiao, H.N., Song, J.L., 2024. Emerging role of additives in lignocellulose enzymatic saccharification: a review. Renew. Sustain. Energy Rev. 197, 114395.
[23]	Liu, Z.C., Madadi, M., Song, G.J., Sun, C.H., Yan, H., Lu, X.M., El-Gendy, N.S., Zhou, Q., Sun, F.B., 2025b Insights into histidine-assisted mitigation of pretreatment-derived inhibitors for sustainable sugar platform biorefinery. J. Environ. Chem. Eng. 13, 119821.
[24]	Madadi, M., Kargaran, E., Hashemi, S.S., Sun, C.H., Denayer, J.F.M., Karimi, K., Sun, F.B., Gupta, V.K., 2025a. Scalable lignin monomer production via machine learning-guided reductive catalytic fractionation of lignocellulose. Adv. Sci. 12, e10496.
[25]	Madadi, M., Saleknezhad, M., Hashemi, S.S., Kargaran, E., Abbasi-Riyakhuni, M., Cai, D., Priyadarshini, A., Elsayed, M., Sun, C.H., Sun, F.B., 2025b Sustainable poplar biorefinery producing butanol-rich solvents, furfural, and lignin-derived compounds with environmental and economic benefits. Biofuel Res. J. 12, 2554–2568.
[26]	Mohamed, A., Visco, D.P. Jr, Breimaier, K., Bastidas, D.M., 2025. Effect of molecular structure on the B3LYP-computed HOMO-LUMO gap: a structure-property relationship using atomic signatures. ACS Omega 10, 2799–2808.
[27]	Oleson, K.R., Sprenger, K.G., Pfaendtner, J., Schwartz, D.T., 2018. Inhibition of the exoglucanase Cel7A by a Douglas-fir-condensed tannin. J. Phys. Chem. B 122, 8665–8674.
[28]	Parr, R.G., Szentpály, L.V., Liu, S.B., 1999. Electrophilicity index. J. Am. Chem. Soc. 121, 1922–1924.
[29]	Parthasarathi, R., Subramanian, V., Roy, D.R., Chattaraj, P.K., 2004. Electrophilicity index as a possible descriptor of biological activity. Bioorg. Med. Chem. 12, 5533–5543.
[30]	Pearson, R.G., 1963. Hard and soft acids and bases. J. Am. Chem. Soc. 85, 3533–3539.
[31]	Roy, K., Kabir, H., 2012. QSPR with extended topochemical atom (ETA) indices: modeling of critical micelle concentration of non-ionic surfactants. Chem. Eng. Sci. 73, 86–98.
[32]	Salentin, S., Schreiber, S., Haupt, V.J., Adasme, M.F., Schroeder, M., 2015. PLIP: fully automated protein-ligand interaction profiler. Nucleic Acids Res. 43, W443–W447.
[33]	Shen, G.N., Yuan, X.C., Cheng, Y., Chen, S.T., Xu, Z.X., Jin, M.J., 2023. Densification pretreatment with a limited deep eutectic solvent triggers high-efficiency fractionation and valorization of lignocellulose. Green Chem. 25, 8026–8039.
[34]	Song, G.J., Liu, D., Madadi, M., Liu, L., Li, C.Y., Liu, Q.Q., Sun, C.H., Zhang, E.Z., Ashori, A., Sun, F.B., 2025. Surfactant-aided acid glycerol pretreatment of sugarcane bagasse: dual benefits of substrate and lignin modifications for improved enzymatic hydrolysis. Energy 320, 135520.
[35]	Song, G.J., Zhang, H., Madadi, M., Chen, Z., Wang, H., Xia, A., Samimi, A., Sun, C.H., Meng, X.Z., Ragauskas, A.J., Sun, F.B., 2024. Unraveling the secrets of harnessing a surfactant-modified strategy in organosolv pretreatment of lignocellulosic biomass for efficient fermentable sugar production. Green Chem. 26, 10123–10138.
[36]	Wang, X., Liu, Y., Luo, S.Y., Liu, B.J., Yao, S.Q., Qin, C.R., Wang, S.F., Liang, C., 2025. Structural characteristics of hemicelluloses and lignin-carbohydrate complexes in alkaline-extracted bamboo green, core, and yellow. J. Bioresour. Bioprod. 10, 386–396.
[37]	Yi, Y.X., Jin, X.F., Chen, M.T., Coldea, T.E., Zhao, H.F., 2024. Surfactant-mediated bio-manufacture: a unique strategy for promoting microbial biochemicals production. Biotechnol. Adv. 73, 108373.
[38]	Yuan, S.L., Cai, Z.T., Xu, G.Y., Jiang, Y.S., 2002. Quantitative structure–property relationships of surfactants: prediction of the critical micelle concentration of nonionic surfactants. Colloid Polym. Sci. 280, 630–636.
[39]	Yuan, Y.F., Guo, X.Y., Jiang, B., Wu, W.J., Zhang, T.W., Sweeney, M., Ahmad, M., Jin, Y.C., 2024. Effect of various aromatic compounds with different functional groups on enzymatic hydrolysis of microcrystalline cellulose and alkaline pretreated wheat straw. J. Bioresour. Bioprod. 9, 211–221.
[40]	Yuan, Y.F., Jiang, B., Chen, H., Wu, W.J., Wu, S.F., Jin, Y.C., Xiao, H.N., 2021. Recent advances in understanding the effects of lignin structural characteristics on enzymatic hydrolysis. Biotechnol. Biofuels 14, 205.
[41]	Zajac, A., Kukawka, R., Pawlowska-Zygarowicz, A., Stolarska, O., Smiglak, M., 2018. Ionic liquids as bioactive chemical tools for use in agriculture and the preservation of agricultural products. Green Chem. 20, 4764–4789.
[42]	Zhai, R., Hu, J.G., Jin, M.J., 2022. Towards efficient enzymatic saccharification of pretreated lignocellulose: enzyme inhibition by lignin-derived phenolics and recent trends in mitigation strategies. Biotechnol. Adv. 61, 108044.
[43]	Zhai, R., Hu, J.G., Saddler, J.N., 2016. What are the major components in steam pretreated lignocellulosic biomass that inhibit the efficacy of cellulase enzyme mixtures? ACS Sustainable Chem. Eng. 4, 3429–3436.
[44]	Zhang, H., Li, W.M., Song, G.J., Al Azad, S., Madadi, M., Deng, Z.C., Samimi, A., Sun, C.H., Sun, F.B., 2025. Role of in situ surfactant modification of lignin structure and surface properties during glycerol pretreatment in modulating cellulase-lignin binding affinities. J. Colloid Interface Sci. 687, 786–800.
[45]	Zhang, H.D., Zhang, J.J., Xie, J., Qin, Y.L., 2020. Effects of NaOH-catalyzed organosolv pretreatment and surfactant on the sugar production from sugarcane bagasse. Bioresour. Technol. 312, 123601.