Bioengineered gut bacterium synthesizing levodopa alleviates motor deficits in models of Parkinson's disease.

ABSTRACT: L-3,4-Dihydroxyphenylalanine (L-DOPA), synthesized from L-tyrosine, is a direct precursor to dopamine. L-DOPA is the gold-standard treatment for Parkinson's disease (PD), given orally alongside decarboxylase inhibitors (e.g., benserazide) to enhance bioavailability. However, its chronic daily pulsatile-like delivery is associated with complications. Herein, we show the construction and in vivo efficacy of a programmable, titratable, genetically engineered E. coli Nissle 1917 system (EcN_L-DOPA) that continuously synthesizes L-DOPA from L-tyrosine for systemic distribution. Oral administration of EcN_L-DOPA with benserazide maintains therapeutic plasma L-DOPA concentrations and increases brain dopamine levels. EcN_L-DOPA improves motor performance and limits de

SUBMITTER: Padhi P 

PROVIDER: S-EPMC12671020 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature