*8.6. Microbe Therapy*

Development of bacteria-based drug has been focused over the past decade. In PKU, the exploitation of gu<sup>t</sup> microbiome to facilitate the degradation of Phe from the diet has shown promising results in clinical trials. Synlogic (https://www.synlogictx.com/), a Massachusetts-based biotech, reprogrammed *Escherichia coli* Nissle (EcN)—that has been isolated from human microbiome. The treatment, dubbed SYNB1618, aim to target two pathways. One Phe degradation pathway, where gene *sltA* encoding Phe ammonia lyase was inserted into the EcN chromosome. Gene *sltA* encodes a cytosolic protein, hence *pheP* gene that encodes a Phe transporter was also engineered in EcN. The second pathway was the insertion of *Proteus mirabilis* pma, which encodes L-amino acid deaminase having higher Phe break down capability. Currently SYNB1618 is in phase II clinical trial to evaluate its potential to lower blood Phe in patients with PKU [122,123] (https://clinicaltrials.gov/ Identifier: NCT03516487).
