Zhi-Qiang Zhou, Dao-Quan Jiao, Yining He, En-Hui Zuo, Zhihui Lu, Ge-Ge Chen, Kai Ding, Cheng‐Hua Wang
As a pivotal biocatalyst in sustainable biotechnology, transglutaminase (TGase, EC 2.3.2.13) has emerged as a versatile molecular tool with transformative applications spanning food science, biomedicine, and green materials. This review critically synthesizes the natural diversity, catalytic mechanisms, and structure-activity relationships of TGases across biological kingdoms, highlighting cutting-edge molecular engineering strategies to enhance production efficiency, thermal stability, and catalytic precision. These strategies include promoter design, secretion pathway optimization, pro-peptide modification, and structure-guided rational design. TGase's distinctive protein assembly functionality, enabling texture and structure enhancement, conflicts with industrial scalability due to prohibitive biosynthesis costs, stringent ambient control demands, and unpredictable performance in complex matrices. Concurrently, this review explores frontier applications, including hybrid protein restructuring, dairy matrices stabilization, plant-based food architecture engineering, and functional biodegradable packaging advancement. By integrating enzymological innovation with industrial imperatives, this synthesis positions TGase as a cornerstone for sustainable, resource-efficient food technologies while delineating pivotal research priorities to address current translational gaps.