Research progress on immobilized penicillin G acylase and industrial applications

Immobilized penicillin G acylase (PGA) is a critical industrial biocatalyst for converting penicillin G into 6-aminopenicillanic acid (6-APA), a key intermediate in the synthesis of β-lactam antibiotics. Although various microorganisms can produce penicillin acylases, free PGA is highly susceptible to structural instability and environmental factors such as temperature and pH fluctuations, leading to a significant activity loss. Furthermore, the separation of free enzymes from reaction systems remains technically challenging, increasing operational complexity and cost. To overcome these limitations, immobilization strategies have been extensively explored. Immobilized PGA exhibits superior stability, reusability, and operational robustness, which are highly desirable for industrial applications. These advantages also lead to improved product purity, reduced contamination risks, and economic benefits. However, immobilization does not necessarily improve intrinsic catalytic efficiency, instead, it often involves a trade-off between catalytic activity and stability due to conformational constraints and mass transfer limitations. Although improved catalytic performance is sometimes reported, such enhancement generally reflects apparent activity rather than intrinsic catalytic efficiency. This review systematically summarizes the origins, classification, structure, and catalytic mechanisms of PGA. It also critically evaluates recent progress in immobilization methods, carrier materials, reaction media, enzyme activity regeneration, and reactor design, providing insights into future challenges and opportunities in this field.