Phenylethylisoquinoline alkaloids (PIAs) are medicinally important natural products derived from the 1-phenylethylisoquinoline precursor. Heterologous production of the PIAs remains challenging due to the incomplete elucidation of biosynthetic pathway and the lack of proper microbial cell factory designed for precursor enhancement. In this work, an artificial pathway composed of eight enzymes from different species was established for de novo 1-phenylethylisoquinoline biosynthesis in engineered