Our project focuses on engineering a probiotic platform for hyperuricemia prevention. We registered two key functional parts: urate transporters (e.g.UacT) and uricase enzymes (e.g.UricaseT).
The urate transporter enables efficient uptake of extracellular uric acid, while the uricase enzyme catalyzes its conversion into allantoin, a more soluble and easily excretable metabolite.
These two types of parts work synergistically to achieve "urate transport + degradation. Combined with our previously developed XanQ-based xanthine transport module, they form a "front-end reduction of uric acid precursors + back-end consumption of uric acid" strategy, providing a novel and integrated approach for the prevention and management of hyperuricemia.
| Name | Nickname | Type | Description | Length | RFC |
|---|---|---|---|---|---|
| BBa_2599WCMX 🔗 | Pj23100-B0034-UacT | Composite Part | This composite part consists of the constitutive promoter Pj23100, the standard ribosome binding site B0034, and the UacT gene, which encodes a uric-acid transporter. When expressed in our engineered probiotic E. coli Nissle 1917, this module enables active uptake of extracellular uric acid, thereby enhancing the strain's capacity to reduce intestinal uric-acid levels. UacT shows strong potential as a uric-acid transporter for probiotic applications. For reference, XanQ, a related transporter from the same family, was used in our previous strain YES301 to mediate xanthine uptake. | 1508 | RFC1000 |
| BBa_25DZQ77O 🔗 | Pj23100-B0034-URI | Composite Part | This composite part consists of the strong constitutive promoter Pj23100, the standard ribosome binding site B0034, and the codon-optimized URI gene, which encodes the full-length uricase derived from Bacillus cereus SKIII. When introduced into our engineered probiotic E. coli Nissle 1917, the Pj23100-B0034 regulatory elements drive intracellular expression of URI. This part is intended for building probiotic strains capable of reducing intestinal uric-acid levels, supporting applications in hyperuricemia mitigation and other uric-acid-associated disorders. | 1539 | RFC1000 |
| BBa_25G5BSV4 🔗 | Pj23100-B0034-URIT | Composite Part | This composite part consists of a strong constitutive promoter (Pj23100), the commonly used ribosome binding site B0034, and the gene encoding the optimized, secreted uricase (UricaseT/URIT). When introduced into the engineered probiotic E. coli Nissle 1917, this part drives the constitutive expression and secretion of the truncated uricase, which has improved extracellular release compared with the wild-type enzyme. The secreted UricaseT efficiently catalyzes the oxidation of uric acid to 5-hydroxyisourate, enabling effective degradation of intestinal uric acid. This part can be used in probiotic-based therapeutic systems to reduce intestinal uric acid levels, offering potential for the prevention or treatment of hyperuricemia and related metabolic disorders. | 1032 | RFC1000 |
| BBa_25W93JGX 🔗 | A codon-optimized uricase derived from Bacillus cereus SKIII | Basic Part | This part encodes a codon-optimized uricase (URI) derived from Bacillus cereus SKIII, redesigned for efficient heterologous expression in Escherichia coli. The gene sequence was optimized according to the codon usage preference of E. coli, which significantly enhances its expression level in the bacterial chassis. This optimized URI part enables E. coli-based engineered probiotics to express functional uricase intracellularly, providing the enzymatic activity needed to degrade uric acid. It can be used as a key component in synthetic biology systems aiming at the prevention or treatment of hyperuricemia and related metabolic disorders. | 1479 | RFC10/RFC1000 |
| BBa_25NDRTAB 🔗 | Structurally optimized uricase | Basic Part | A structurally optimized uricase capable of degrading uric acid designed to enhance extracellular secretion. | 972 | RFC10/RFC1000 |
| BBa_25STUJVB 🔗 | UacT_UricAcidTransporter | Basic Part | This part encodes UacT, a putative uric acid transporter belonging to the Nucleobase-Cation Symporter-2 (NCS2) family, the same family as the well-characterized xanthine transporter XanQ (YgfO). UacT is predicted to have strong potential for facilitating the uptake of extracellular uric acid into engineered probiotic cells. In our project, XanQ was used in the engineered probiotic YES301 as a high-efficiency xanthine transporter, whereas UacT represents a promising alternative transporter for targeting uric acid import in similar probiotic chassis. | 1409 | RFC10/RFC1000 |
| BBa_250MXNRM 🔗 | Promoter-RBS designed to drive strong expression of xanthine transporter protein gene | Basic Part | This part consists of a promoter and ribosome binding site (RBS) arranged as a regulatory module designed to drive strong expression of downstream coding sequences. It has been specifically optimized for the efficient translation of xanthine transporter proteins, which play a key role in the uptake of purine metabolites. When assembled upstream of a coding sequence, this promoter-RBS combination provides robust transcriptional initiation and reliable ribosome recruitment, leading to enhanced protein production. In our project, it was used to achieve high-level expression of a xanthine transporter, enabling engineered E. coli Nissle 1917 to efficiently uptake xanthine and related purine compounds. This regulatory part can be used in other contexts where strong constitutive expression of a protein of interest is required. | 60 | RFC1000 |
