O-methyltransferase involved in the biosynthesis of etoposide, a chemotherapeutic compound of the topoisomerase inhibitor family (PubMed:26359402). Catalyzes the methylation of (-)-5'-demethylyatein to produce (-)-yatein (PubMed:26359402). (-)-5'-demethylyatein + S-adenosyl-L-methionine = (-)-yatein + H(+) + S-adenosyl-L-homocysteine Aromatic compound metabolism; phenylpropanoid biosynthesis. Homodimer. Mostly expressed in stems, and, to a lower extent, in leaves. Transiently induced after wounding. Combinatorially expression of Sinopodophyllum hexandrum (mayapple) genes of the podophyllotoxin pathway (e.g. DIR, PLR, SDH, CYP719A23, OMT3, CYP71CU1, OMT1, 2-ODD, CYP71BE54 and CYP82D61) in Nicotiana benthamiana (tobacco) results in the production of the chemotherapeutic compound etoposide. Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-independent O-methyltransferase family. COMT subfamily.