Urate oxidase is considered as an important therapeutic enzyme used to control hyperuricemia.
In spite of widespread distribution in numerous (micro)organisms, active urate oxidase is absent
in higher primates (humans and apes) due to gene mutations. Considering the therapeutic significance
of urate oxidase, further understanding on the inactivation process of the enzyme during primate evolution
is critical. This study, therefore, aims to express genetically modified human urate oxidase in the
methylotrophic yeast Pichia pastoris. Accordingly, the genetically modified human urate oxidase was
successfully expressed intracellularly and extracellularly under the control of an alcohol oxidase promoter
and was subjected to the enzyme activity assay. The results demonstrated that reactivating the non-functional human
urate oxidase gene fully or even moderately by simply replacing the premature stop codons is impossible. This finding
confirms the idea that a number of successive loss-of-function missense mutations occurred during evolution, making
higher primates functional uricase-deficit and vulnerable to hyperuricemic disorders.
Keywords: Expression, hominoid evolution, Pichia pastoris, pseudogene, urate oxidase, uricase.
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