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Biosynthesis of the Structurally Unique Polycyclopropanated Polyketide–Nucleoside Hybrid Jawsamycin (FR‐900848)
Author(s) -
Hiratsuka Tomoshige,
Suzuki Hideaki,
Kariya Ryo,
Seo Takashi,
Minami Atsushi,
Oikawa Hideaki
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201402623
Subject(s) - polyketide , polyketide synthase , gene cluster , biosynthesis , heterologous expression , stereochemistry , gene , enzyme , biochemistry , chemistry , computational biology , biology , recombinant dna
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.