Rationalization design, soluble expression and PEG modification of highly active recombinant human-porcine uricase mutant protein.

Autor: Tong M; Institute of Biomedicine and National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, People's Republic of China. Electronic address: 2294089306@qq.com., Wang S; Institute of Biomedical Transformation, School of Basic Medicine and Public Health, Jinan University, Guangzhou 510632, People's Republic of China. Electronic address: 237769493@qq.com., Luan J; Institute of Biomedicine and National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, People's Republic of China. Electronic address: 981467216@qq.com., Xie Q; Institute of Biomedicine and National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, People's Republic of China; Guangdong JNU Genetic Medicine Engineering Research Center Co. Ltd, Guangzhou 510530, People's Republic of China. Electronic address: txql@jnu.edu.cn., Wang L; 13F, Bldg. D, Runhui Sci-Tech Park, 18 Shenzhou Rd., Science City, Huangpu Dist., Vibrant Therapeutics, Guangzhou 510663, People's Republic of China. Electronic address: lwang@vibrantx.io., Shen X; Beijing Chemgen Pharma Co.Ltd District 1, Building B, No.12 Hongda North Road, Jingkai District, Beijing 100176, People's Republic of China. Electronic address: sales1@chemgenpharma.com., Xiong S; Institute of Biomedicine and National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, People's Republic of China; Guangdong JNU Genetic Medicine Engineering Research Center Co. Ltd, Guangzhou 510530, People's Republic of China. Electronic address: xsh_jnu@hotmail.com.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Jun; Vol. 269 (Pt 1), pp. 131989. Date of Electronic Publication: 2024 Apr 30.
DOI: 10.1016/j.ijbiomac.2024.131989
Abstrakt: Uric acid is the end product of purine metabolism in humans due to inactivation of the uricase determined by the mutated uricase gene. Uricase catalyzes the conversion of uric acid into water-soluble allantoin that is easily excreted by the kidneys. Hyperuricemia occurs when the serum concentration of uric acid exceeds its solubility (7 mg/dL). However, modifications to improve the uricase activity is under development for treating the hyperuricemia. Here we designed 7 types of human-porcine chimeric uricase by multiple sequence comparisons and targeted mutagenesis. An optimal human-porcine chimeric uricase mutant (uricase-10) with both high activity (6.33 U/mg) and high homology (91.45 %) was determined by enzyme activity measurement. The engineering uricase was further modified with PEGylation to improve the stability of recombinant protein drugs and reduce immunogenicity, uricase-10 could be more suitable for the treatment of gout and hyperuricemia theoretically.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
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Databáze: MEDLINE
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