10.1021/jacs.8b02769.s001
Hayama Tsutsumi
Hayama
Tsutsumi
Yohei Katsuyama
Yohei
Katsuyama
Miho Izumikawa
Miho
Izumikawa
Motoki Takagi
Motoki
Takagi
Manabu Fujie
Manabu
Fujie
Noriyuki Satoh
Noriyuki
Satoh
Kazuo Shin-ya
Kazuo
Shin-ya
Yasuo Ohnishi
Yasuo
Ohnishi
Unprecedented
Cyclization Catalyzed by a Cytochrome
P450 in Benzastatin Biosynthesis
American Chemical Society
2018
cytochrome P 450 nitrene transferase
cyclization
enzyme
RI
tetrahydroquinoline scaffolds
acid
benzastatin biosynthetic gene cluster
geranylated p
Unprecedented Cyclization Catalyzed
indoline
Benzastatin Biosynthesis Benzastatins
cytochrome P 450
Cytochrome P 450
BezE catalyzes elimination
2018-05-02 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Unprecedented_Cyclization_Catalyzed_by_a_Cytochrome_P450_in_Benzastatin_Biosynthesis/6294287
Benzastatins
have unique structures probably derived from geranylated <i>p</i>-aminobenzoic acids. The indoline and tetrahydroquinoline
scaffolds are presumably formed by cyclization of the geranyl moiety,
but the cyclization mechanism was unknown. We studied the benzastatin
biosynthetic gene cluster of <i>Streptomyces</i> sp. RI18;
functions of the six enzymes encoded by it were analyzed by gene disruption
in a heterologous host and in vitro enzyme assays. We propose the
biosynthetic pathway for benzastatins in which a cytochrome P450 (BezE)
is responsible for the cyclization of geranylated <i>p</i>-acetoxyaminobenzoic acids; BezE catalyzes elimination of acetic
acid to form an iron nitrenoid, nitrene transfer to form an aziridine
ring, and nucleophilic addition of hydroxide ion to C-10 and chloride
ion to C-9 to generate the indoline and tetrahydroquinoline scaffolds,
respectively. Discovery of this enzyme, which should be termed cytochrome
P450 nitrene transferase, provides an important insight into the functional
diversity of cytochrome P450.