RESUMEN
Uric acid, the end product of purine degradation, causes hyperuricemia and gout, afflicting hundreds of millions of people. The debilitating effects of gout are exacerbated by dietary purine intake, and thus a potential therapeutic strategy is to enhance purine degradation in the gut microbiome. Aerobic purine degradation involves oxidative dearomatization of uric acid catalyzed by the O2-dependent uricase. The enzymes involved in purine degradation in strictly anaerobic bacteria remain unknown. Here we report the identification and characterization of these enzymes, which include four hydrolases belonging to different enzyme families, and a prenyl-flavin mononucleotide-dependent decarboxylase. Introduction of the first two hydrolases to Escherichia coli Nissle 1917 enabled its anaerobic growth on xanthine as the sole nitrogen source. Oral supplementation of these engineered probiotics ameliorated hyperuricemia in a Drosophila melanogaster model, including the formation of renal uric acid stones and a shortened lifespan, providing a route toward the development of purinolytic probiotics.
Asunto(s)
Gota , Hiperuricemia , Humanos , Animales , Ácido Úrico/metabolismo , Anaerobiosis , Drosophila melanogaster/metabolismo , Gota/metabolismo , Purinas/metabolismo , Escherichia coli/metabolismo , Hidrolasas/metabolismoRESUMEN
The TFIIB-related factor (BRF) family plays vital roles in RNA polymerase (Pol) III transcription initiation. However, little is known about the role of BRF in plants. Here, we report BRF1 and BRF2 are involved in Arabidopsis reproduction. In this study, we generated BRF1 and BRF2 double mutant plants. We found that no homozygous double mutants of brf1brf2 were obtained when brf1 and brf2 were crossed, although brf1 and brf2 mutants individually developed and reproduced normally. Further experiments revealed that heterozygous brf1/ + brf2/ + produced abnormal pollen and had no seeds in some placentas of siliques. Genetic data derived from reciprocal crosses showed that BRF2 plays a dominant role in Arabidopsis reproduction. Taken together, a double mutation of BRF1 and BRF2 results in a high degree of aborted macrogametes and microgametes and complete failure in zygote generation, ultimately leading to sterility.