Biosynthetic gene cluster identification and biological activity of lucilactaene from Fusarium sp. RK97-94

Sho Kato; Takayuki Motoyama; Yushi Futamura; Masakazu Uramoto; Toshihiko Nogawa; Toshiaki Hayashi; Hiroshi Hirota; Akira Tanaka; Naoko Takahashi-Ando; Takashi Kamakura; Hiroyuki Osada

doi:10.1080/09168451.2020.1725419

Biosynthetic gene cluster identification and biological activity of lucilactaene from Fusarium sp. RK97-94

Biosci Biotechnol Biochem. 2020 Jun;84(6):1303-1307. doi: 10.1080/09168451.2020.1725419. Epub 2020 Feb 11.

Authors

Sho Kato^{1

2}, Takayuki Motoyama¹, Yushi Futamura¹, Masakazu Uramoto¹, Toshihiko Nogawa¹, Toshiaki Hayashi¹, Hiroshi Hirota¹, Akira Tanaka^{1

3}, Naoko Takahashi-Ando^{3

4}, Takashi Kamakura⁵, Hiroyuki Osada^{1

2}

Affiliations

¹ Chemical Biology Research Group, RIKEN CSRS, Wako, Saitama, Japan.
² Graduate School of Science and Engineering, Saitama University, Sakura, Saitama, Japan.
³ Graduate School of Science and Engineering, Toyo University, Kawagoe, Saitama, Japan.
⁴ Graduate School of Engineering, Toyo University, Kawagoe, Saitama, Japan.
⁵ Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba, Japan.

PMID: 32043422
DOI: 10.1080/09168451.2020.1725419

Abstract

We identified the biosynthetic gene cluster for lucilactaene, a cell cycle inhibitor from a filamentous fungus Fusarium sp. RK 97-94. The luc1 knockout strain accumulated demethylated analogs, indicating the involvement of Luc1 methyltransferase in lucilactaene biosynthesis. Lucilactaene showed potent antimalarial activity. Our data suggested that methylation and ether ring formation are essential for its potent antimalarial activity.

Keywords: Natural products; PKS-NRPS; biological activity; biosynthesis; malaria.

MeSH terms

Antimalarials / metabolism*
Antimalarials / pharmacology
Cell Cycle / drug effects
Fungal Proteins / genetics
Fungal Proteins / metabolism
Furans / metabolism*
Furans / pharmacology
Fusarium / genetics*
Fusarium / metabolism*
Gene Knockout Techniques
Methylation
Methyltransferases / genetics
Methyltransferases / metabolism
Microorganisms, Genetically-Modified
Multigene Family*
Pyrroles / metabolism*
Pyrroles / pharmacology

Substances

Antimalarials
Fungal Proteins
Furans
Pyrroles
lucilactaene
Methyltransferases