A biosynthetic pathway to fungal polyketide-nonribosomal peptide natural products, Sch210971 (1a) and Sch210972 (1b) from Hapsidospora irregularis, was characterized by reconstitution and heterologous expression in Fusarium heterosporum. Using genetic, biochemical, and feeding experiments, we show that the incorporated amino acid 4-hydroxyl-4-methyl glutamate (HMG) is synthesized by an aldolase, probably using pyruvate as the precursor.