Synthetic Biology

Synthesizing a therapeutic probiotic

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Science  07 Sep 2018:
Vol. 361, Issue 6406, pp. 988
DOI: 10.1126/science.361.6406.988-b

Phenylketonuria is a disease caused by an inability to metabolize the amino acid phenylalanine, which can accumulate in the blood and brain, causing neurotoxicity. Patients are treated by restricting phenylalanine intake through a low-protein diet, but this can cause failure to thrive. To improve the therapeutic options, Isabella et al. developed a probiotic that meets the current requirements for clinical testing. They engineered a strain of Escherichia coli with a strong safety profile in humans to inducibly express a phenylalanine-degrading enzyme. Oral administration of this probiotic in a mouse model of phenylketonuria prevented increased phenylalanine concentrations in the blood when the mice were injected with phenylalanine, suggesting that gastrointestinal degradation can regulate circulating phenylalanine concentrations. Thus, this synthetic probiotic could have potential in clinical trials.

Nat. Biotechnol. 10.1038/nbt.4222 (2018).

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