Biosynthesis of the structurally unique polycyclopropanated polyketide-nucleoside hybrid jawsamycin (FR-900848).
The biosynthetic gene cluster of antifungal agent jawsamycin (FR-900848) has been identified by heterologous expression. A series of gene inactivations and in vitro and in vivo analysis of key enzymes in the biosynthetic pathway established their functions. A novel mechanism involving a radical S-adenosyl methionine (SAM) cyclopropanase collaborating with an iterative polyketide synthase is proposed for the construction of the unique polycyclopropanated backbone. Our reconstitution system sets the stage for studying the catalytic mechanism of this intriguing contiguous cyclopropanation.
Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810 (Japan).
Tomoshige
T
Hiratsuka
Hideaki
H
Suzuki
Ryo
R
Kariya
Takashi
T
Seo
Atsushi
A
Minami
Hideaki
H
Oikawa
D000935:Antifungal Agents / Q000737:chemistry / Q000378:metabolism*; D003521:Cyclopropanes / Q000737:chemistry; D005810:Multigene Family; D009705:Nucleosides / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D048630:Polyketide Synthases / Q000378:metabolism; D061065:Polyketides / Q000737:chemistry / Q000378:metabolism*; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism
D000935:Antifungal Agents; D003521:Cyclopropanes; D009705:Nucleosides; D061065:Polyketides; C065437:FR 900848; D048630:Polyketide Synthases
antifungal agents; biosynthesis; natural products; polycyclopropanes; polyketides