Live Biotherapeutics Drug Discovery Service for Phenylketonuria Disease


Phenylketonuria (PKU) is an inborn error in the metabolism of phenylalanine (phe) and tyrosine (Tyr). It is an autosomal recessive disease caused by a deficiency of the liver enzyme phenylalanine hydroxylase (PAH). Patients with PKU are unable to metabolize the amino acid phe, resulting in its accumulation throughout the body. If left untreated, elevated Phe levels can lead to severe neurological complications and disability. The goal of PKU treatment is to reduce blood phe to a level that allows normal brain development. Metabolic disorders, such as PKU require lifelong treatment. Therefore, the development of low-cost and easy-to-administer therapeutic strategies is essential to increase individual compliance with treatment to increase their effectiveness. Next-generation probiotics are living biotherapeutics that have been genetically engineered to target specific diseases. It is now possible to engineer the composition of therapeutic molecules or enzymes expressing probiotics with multiple beneficial properties, potentially increasing their potential beneficial effects against a wider range of diseases. In the case of individuals with PKU, a new option for their treatment is the use of genetically modified probiotics, which is a scientific advancement in genetic engineering, for the production and release of metabolic enzymes effective in reducing blood concentrations of Phe. PKU is another example of a metabolic disorder that may benefit from the use of probiotics to deliver the PAL enzyme to the gut.

Next-Generation Probiotics Therapy

  • Genetically Modified (GM) Probiotic for the Production of Metabolic Enzymes
    The use of GM probiotics as live biotherapeutic agents to treat specific diseases is a complex alternative therapeutic strategy. There is increasing evidence that live biotherapeutics consisting of engineered microorganisms (synthetic biologics) can be used to sense and respond to environmental signals in humans to metabolize potentially toxic compounds, including plate heat exchangers. Using genetically engineered probiotics, efficacy was shown both in vitro and in vivo. These probiotics could meet the need for new drugs for PKU treatment. In a study using transgenic probiotics expressing metabolic enzymes, E. coli expressing urease from Klebsiella aerogenes significantly reduced plasma urea, uric acid, and creatinine in rats with experimental renal failure.
  • GM Probiotic For the Delivery of Metabolic Enzymes
    Phenylalanine ammonia-lyase (PAL) is used as enzyme substitution therapy. Maintaining enzyme stability is a big issue that can be overcome by using encapsulation or using live microorganisms as a delivery system. Enzyme-substitution therapies (EST) have demonstrated promise in pre-clinical and clinical settings by providing a metabolic sink for phe in PKU. Recently, the ability to deliver ESTs by oral administration has been achieved through the use of engineered probiotics - living therapeutics. The use of probiotics like lactobacillus and genetically modified probiotics in transporting and delivering PAL have also gained attention and tried.
  • Natural Probiotics
    The supplementation with probiotics encoding for enzymes can drive Trp metabolism towards 5-HT synthesis. Probiotics may be a therapeutic strategy to help degrade dietary phe, reducing its levels before ingestion.

Fig.1 An overview of how probiotics can improve symptoms of PKU. (de, 2022)Fig.1 An overview of how probiotics can improve symptoms of PKU.1

Our Services for PKU Research

Research Articles Available Services
Genetically engineered probiotic for the treatment of PKU; assessment of a novel treatment in vitro and in the PAHenu2 mouse model of PKU.2
Adaptive Strategies of the Candidate Probiotic E. coli Nissle in the Mammalian Gut.3

Probiotic strains are attractive for the development of biotherapeutics. For developing successful therapies for the treatment of PKU, it is important to consider characteristics such as genetic stability. More studies are needed to validate the use of these next-generation probiotics in humans, assess the effect of probiotic therapy on gut microbiota composition, and ensure their safety because they are genetically modified organisms. E. coli Nissle is an important strain that has been studied for the development of engineering therapies for PKU because it presents an excellent safety profile and genetic tractability. Creative Biolabs has a strong technical background in engineering strain construction and safety assessment. Please feel free to contact us to discuss your project, and we are happy to provide you with professional technical insights.


  1. De Oliveira Filho, Josemar Gonçalves, et al. "Next-generation probiotics as a therapeutic strategy for the treatment of phenylketonuria: a review." Nutrition Reviews 80.10 (2022): 2100-2112.
  2. Durrer, Katherine E., Michael S. Allen, and Ione Hunt von Herbing. "Genetically engineered probiotic for the treatment of phenylketonuria (PKU); assessment of a novel treatment in vitro and in the PAHenu2 mouse model of PKU." PloS one 12.5 (2017): e0176286.
  3. Crook, Nathan, et al. "Adaptive strategies of the candidate probiotic E. coli Nissle in the mammalian gut." Cell host & microbe 25.4 (2019): 499-512.

For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.

Online Inquiry

For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.

Contact us

Live Biotherapeutic

Contact us

Copyright © 2024 Creative Biolabs. All Rights Reserved.

Inquiry Basket