Safety and uric acid-lowering performance of engineered food-grade Lactococcus lactis: A novel candidate for hyperuricemia functional food development

Hyperuricemia and gout have evolved into a global health burden, necessitating the development of innovative approaches for their long-term dietary management. In this study, food-grade Lactococcus lactis was genetically engineered by introducing urate oxidase (UOX) genes from GRAS strains, to construct novel engineered lactic acid bacteria (LAB) with biosafety and UA-lowering performance. The results showed that the engineered LAB possessed excellent uric acid (UA) degradation ability. The specific UOX activities of L. lactis NZ3900/pNZ8149- pucL and L. lactis NZ3900/pNZ8149- CuUOX were (21.38 ± 0.17) U/mg and (28.06 ± 0.44) U/mg, respectively. High-performance liquid chromatography (HPLC) detection revealed that their degradation rates against 1 mmol/L UA reached 82.16% ± 4.39% and 35.48% ± 1.13% at 3 h. An in vitro Transwell model further validated their capacity for UA absorption and transport. Hemolytic activity and antibiotic susceptibility assessments indicated the favorable biosafety of the engineered LAB. This novel UA-lowering engineered LAB offers a promising candidate for developing functional foods and probiotic dietary preparations to prevent and alleviate hyperuricemia and gout.