%0 Journal Article
%A Tsutsumi, Hayama
%A Katsuyama, Yohei
%A Izumikawa, Miho
%A Takagi, Motoki
%A Fujie, Manabu
%A Satoh, Noriyuki
%A Shin-ya, Kazuo
%A Ohnishi, Yasuo
%D 2018
%T Unprecedented
Cyclization Catalyzed by a Cytochrome
P450 in Benzastatin Biosynthesis
%U https://acs.figshare.com/articles/journal_contribution/Unprecedented_Cyclization_Catalyzed_by_a_Cytochrome_P450_in_Benzastatin_Biosynthesis/6294287
%R 10.1021/jacs.8b02769.s001
%2 https://acs.figshare.com/ndownloader/files/11516072
%K cytochrome P 450 nitrene transferase
%K cyclization
%K enzyme
%K RI
%K tetrahydroquinoline scaffolds
%K acid
%K benzastatin biosynthetic gene cluster
%K geranylated p
%K Unprecedented Cyclization Catalyzed
%K indoline
%K Benzastatin Biosynthesis Benzastatins
%K cytochrome P 450
%K Cytochrome P 450
%K BezE catalyzes elimination
%X Benzastatins
have unique structures probably derived from geranylated p-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 Streptomyces 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 p-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.
%I ACS Publications