Biosynthesis of the Fusarium Mycotoxin (-)-Sambutoxin.

4-Hydroxy-2-pyridone alkaloids have attracted attention for synthetic and biosynthetic studies due to their broad biological activities and structural diversity. Here, we elucidated the pathway and chemical logic of (-)-sambutoxin (1) biosynthesis. In particular, we uncovered the enzymatic origin of the tetrahydropyran moiety and showed that the p-hydroxyphenyl group is installed via a late-stage, P450-catalyzed oxidation of the phenylalanine-derived side chain rather than via a direct incorporation of tyrosine.