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

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

  • J Antibiot (Tokyo). 2022 Jul;75(7):361-374. doi: 10.1038/s41429-022-00529-3.
Islam A Abdelhakim 1 2 3 4,  Takayuki Motoyama 1,  Toshihiko Nogawa 1,  Fauze Bin Mahmud 1 5 6,  Yushi Futamura 1,  Shunji Takahashi 2 3,  Hiroyuki Osada 7 8
Affiliations

Affiliations

  • 1 Chemical Biology Research Group, RIKEN CSRS, Wako, Saitama, Japan.
  • 2 Natural Product Biosynthesis Research Unit, RIKEN CSRS, Wako, Saitama, Japan.
  • 3 Graduate School of Science and Engineering, Saitama University, Sakura, Saitama, Japan.
  • 4 Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
  • 5 Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang, Malaysia.
  • 6 Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Sabah, Malaysia.
  • 7 Chemical Biology Research Group, RIKEN CSRS, Wako, Saitama, Japan. cb-secretary@ml.riken.jp.
  • 8 Chemical Resource Development Research Unit, RIKEN CSRS, Wako, Saitama, Japan. cb-secretary@ml.riken.jp.
PMID: 35484225 DOI: 10.1038/s41429-022-00529-3
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.

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