Production of Kinanthraquinone D with Antimalarial Activity by Heterologous Gene Expression and Biotransformation in Streptomyces lividans TK23.

Two new compounds, kinanthraquinone C ( 1 ) and kinanthraquinone D ( 2 ), were isolated along with two known compounds, kinanthraquinone ( 3 ) and kinanthraquinone B ( 4 ), produced by the heterologous expression of the kiq biosynthetic gene cluster and its pathway-specific regulator, kiqA , in Streptomyces lividans TK23. The chemical structures of compounds 1 and 2 were determined using mass spectrometry and nuclear magnetic resonance analyses. To examine a biosynthetic pathway of compounds 1 and 2 , incubation experiments were conducted using S. lividans TK23 to supply the compounds 3 and 4 . These experiments indicated that compounds 3 and 4 were converted to compounds 2 and 1 , respectively, by the endogenous enzymes of S. lividans TK23. Compounds 2 , 3 , and 4 had antimalarial activities at half-maximal inhibitory concentration values of 0.91, 1.2, and 15 μM, respectively, without cytotoxicity up to 30 μM.