Isolation of new lucilactaene derivatives from P450 monooxygenase and aldehyde dehydrogenase knockout Fusarium sp. RK97-94 strains and their biological activities

Fusarium sp. RK97-94 is a producer of potent antimalarial compounds such as lucilactaene and its derivatives. The biosynthetic gene cluster of lucilactaene was identified but only a knockout mutant of methyltransferase ( luc1 ) was reported in previous papers. Herein, we report on isolation and identification of prelucilactaene G ( 1 ), and prelucilactaene H ( 2 ) from the aldehyde dehydrogenase knockout strain (∆ luc3 ) culture broth, as well as prelucilactaene A ( 3 ), prelucilactaene B ( 4 ), and two isomeric mixtures of prelucilactaene E ( 5 ) and prelucilactaene F ( 6 ), from the P450 monooxygenase knockout strain (∆ luc2 ) culture broth. Our data, unlike the previous ones, suggest the involvement of the aldehyde dehydrogenase (Luc3) in lucilactaene biosynthesis, and support the involvement of the P450 monooxygenase (Luc2) in C-20 hydroxylation rather than C-13–C-14 epoxidation or C-15 hydroxylation. Isolated compounds displayed moderate to strong antimalarial activities, and the structure–activity relationship of lucilactaene derivatives was examined.