Yaereen Dho

Abstract Homoharringtonine (HHT) is a plant-derived protein translation inhibitor used widely in ribosomal profiling and as a treatment for chronic myeloid leukemia approved by the US Food and Drug Administration. HHT is commercially semisynthesized from the alkaloid core cephalotaxine (CET) extracted from endangered Cephalotaxus species. Despite its importance, the CET/HHT biosynthetic pathway remains unresolved.

Abstract Plants produce diverse molecules that inhibit protein translation. A lead example is homoharringtonine (HHT), a key tool for ribosomal profiling and an FDA-approved treatment for chronic myeloid leukemia. HHT is commercially produced through semi-synthesis from the alkaloid core cephalotaxine (CET) extracted from endangered Cephalotaxus species. Despite its significance, the CET/HHT biosynthetic pathway remains unresolved.

Abstract Plants synthesize numerous alkaloids that mimic animal neurotransmitters1. The diversity of alkaloid structures is achieved through the generation and tailoring of unique carbon scaffolds2,3, yet many neuroactive alkaloids belong to a scaffold class for which no biosynthetic route or enzyme catalyst is known.