ArticleScience China. Life sciences2023
Expression of phenylalanine ammonia lyase as an intracellularly free and extracellularly cell surface-immobilized enzyme on a gut microbe as a live biotherapeutic for phenylketonuria.
Article in Science China. Life sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- Minicells derived fromApplied and environmental microbiology · 2026Article
- Gut microbiota in genetic diseases: from Mendelian disorders to complex traits.Frontiers in immunology · 2026Review
- CRISPR-Assisted Probiotic and In Situ Engineering of Gut Microbiota: A Prospect to Modification of Metabolic Disorders.Probiotics and antimicrobial proteins · 2026Review
- Gut microbiota-mediated modulation of host amino acid availability and metabolism.Gut microbes · 2025Review
- Recent advances of engineered probiotics for therapeutic applications.Biodesign research · 2025Review
- Potential applications of engineered bacteria in disease diagnosis and treatment.Microbiome research reports · 2025Review
- Engineering probioticApplied and environmental microbiology · 2024Article
- Engineered Probiotics for the Management of Congenital Metabolic Diseases: A Systematic Review.Preventive nutrition and food science · 2024Review
- Phenylalanine diminishes M1 macrophage inflammation.Science China. Life sciences · 2023Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phenylketonuria (PKU), a disease resulting in the disability to degrade phenylalanine (Phe) is an inborn error with a 1 in 10,000 morbidity rate on average around the world which leads to neurotoxicity. As an potential alternative to a protein-restricted diet, oral intake of engineered probiotics degrading Phe inside the body is a promising treatment, currently at clinical stage II (Isabella, et al., 2018). However, limited transmembrane transport of Phe is a bottleneck to further improvement of the probiotic's activity. Here, we achieved simultaneous degradation of Phe both intracellularly and extracellularly by expressing genes encoding the Phe-metabolizing enzyme phenylalanine ammonia lyase (PAL) as an intracellularly free and a cell surface-immobilized enzyme in Escherichia coli Nissle 1917 (EcN) which overcomes the transportation problem. The metabolic engineering strategy was also combined with strengthening of Phe transportation, transportation of PAL-catalyzed trans-cinnamic acid and fixation of released ammonia. Administration of our final synthetic strain TYS8500 with PAL both displayed on the cell surface and expressed inside the cell to the Pah
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