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

Islam A. Abdelhakim, Takayuki Motoyama, Toshihiko Nogawa, Fauze Bin Mahmud, Yushi Futamura, Shunji Takahashi, Hiroyuki Osada*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)361-374
Number of pages14
JournalJournal of Antibiotics
Volume75
Issue number7
DOIs
Publication statusAccepted/In press - 2022

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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