Enzymatic detoxification mechanisms of histamine in fish and fermented aquatic products: research progress and future development strategies.

Histamine is a biogenic amine and a chemical food safety hazard in fish and fermented aquatic products. Prevention and enzymatic degradation are complementary strategies. This review compares the catalytic mechanisms of diamine oxidase, histamine dehydrogenase, multicopper oxidase and glyceraldehyde-3-phosphate dehydrogenase, the latter as a moonlighting enzyme with limited histamine-degrading activity. Building on these mechanisms, we evaluate kinetic limitations from high salinity, low pH, and competing amines in fish and fermented aquatic products, including fish sauce and canned tuna homogenates, although final-product validation remains lacking. Food-grade immobilization and whole-cell biocatalysis are discussed as current or applied approaches, while AI-guided protein design and micro-/nanomotor systems remain at proof-of-concept or early-development stages. Despite progress in understanding histamine-degrading enzymes, application remains hindered by short enzymatic half-lives, process incompatibility, and inhibitor vulnerability. We propose a conceptual multi-hurdle framework centered on enzymatic degradation and complementary supply-chain measures, shifting seafood safety from reactive monitoring toward proactive control.