Issue 27, 2025

Engineered pH-buffering nanocomposite for robust one-pot multi-enzyme cascade synthesis of γ-aminobutyric acid

Abstract

Enzyme catalysis has emerged as a green platform for synthesizing high-value pharmaceuticals and fine chemicals, leveraging its inherent selectivity and sustainability. However, enzymatic cascade systems for valuable chemical synthesis face significant challenges, including dependence on expensive cofactors, catalytic incompatibility between enzymes, and limited stability. Herein, we develop an engineered pH-buffering nanocomposite for robust one-pot three-enzyme cascade synthesis of γ-aminobutyric acid. A composite material integrating pH-responsive poly(methacrylic acid) with a zeolitic imidazolate framework-8 was employed for the in situ encapsulation of enzymes. This strategy enables glutamate decarboxylase, which requires acidic conditions, to function efficiently in a neutral environment. We demonstrate the superior capability of this nanocomposite in resolving pH incompatibility in multi-enzyme cascade systems. With the highly efficient cofactor regeneration of formate dehydrogenase, α-ketoglutaric acid is catalyzed to γ-aminobutyric acid via a cascade involving glutamate dehydrogenase and glutamate decarboxylase with a rate of 2.34 mM h−1. The nanocomposite establishes localized acidic microenvironments under neutral bulk conditions (pH 7.0), enabling synchronized NADH regeneration with a total turnover number of 662 and conversion efficiency of 93.6% of α-ketoglutarate to γ-aminobutyric acid in a one-pot system. This approach offers a scalable and cost-effective biocatalytic strategy for structurally complex molecules, advancing sustainable pharmaceutical manufacturing.

Graphical abstract: Engineered pH-buffering nanocomposite for robust one-pot multi-enzyme cascade synthesis of γ-aminobutyric acid

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Article information

Article type
Paper
Submitted
22 Apr 2025
Accepted
09 Jun 2025
First published
10 Jun 2025

Green Chem., 2025,27, 8216-8225

Engineered pH-buffering nanocomposite for robust one-pot multi-enzyme cascade synthesis of γ-aminobutyric acid

H. Luo, T. P. Lai, Y. Gao, W. Li, Y. Fan and L. Zhang, Green Chem., 2025, 27, 8216 DOI: 10.1039/D5GC02022K

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