Mutasynthesis of Fluorinated Pactamycin Analogues and their Antimalarial Activity

A mutasynthetic strategy has been used to generate fluorinated TM-025 and TM-026, two biosynthetically engineered pactamycin analogues produced by a mutant strain of Streptomyces pactum. The compounds were produced by blocking the formation of the pactamycin biosynthetic precursor 3-aminobenzoic acid and performing precursor-directed structure modification. The fluorinated compounds maintain excellent activity and selectivity toward chloroquine-sensitive and multidrug-resistant strains of malarial parasites as the parent compounds. The results also provide insights into the biosynthesis of 3-aminobenzoic acid in S. pactum.