Complete biosynthetic pathways for cephalotaxinone and homoerythratine were elucidated from the endangered plant Cephalotaxus fortunei. Thirteen key enzymes were identified, including two homologous cytochrome P450 enzymes that catalyze a rare divergent oxidation process governing alkaloid scaffold diversification. Full pathway reconstitution in Nicotiana benthamiana establishes a foundation for the sustainable production of the anticancer agent homoharringtonine.