13252-71-6Relevant articles and documents
Characterization of the N-oxygenase AurF from Streptomyces thioletus
Chanco, Emmanuel,Choi, Yoo Seong,Sun, Ning,Vu, Michael,Zhao, Huimin
, p. 5569 - 5577 (2014)
AurF catalyzes the N-oxidation of p-aminobenzoic acid to p-nitrobenzoic acid in the biosynthesis of the antibiotic aureothin. Here we report the characterization of AurF under optimized conditions to explore its potential use in biocatalysis. The pH optimum of the enzyme was established to be 5.5 using phenazine methosulfate (PMS)/NADH as the enzyme mediator system, showing ~10-fold higher activity than previous reports in literature. Kinetic characterization at optimized conditions give a Km of 14.7 ± 1.1 μM, a kcat of 47.5 ± 5.4 min-1 and a kcat/Km of 3.2 ± 0.4 μM-1 min-1. PMS/NADH and the native electron transfer proteins showed significant formation of the p-hydroxylaminobenzoic acid intermediate, however H2O2 produced mostly p-nitrobenzoic acid. Alanine scanning identified the role of important active site residues. The substrate specificity of AurF was examined and rationalized based on the protein crystal structure. Kinetic studies indicate that the Km is the main determinant of AurF activity toward alternative substrates.
Unprecedented Cyclization Catalyzed by a Cytochrome P450 in Benzastatin Biosynthesis
Tsutsumi, Hayama,Katsuyama, Yohei,Izumikawa, Miho,Takagi, Motoki,Fujie, Manabu,Satoh, Noriyuki,Shin-Ya, Kazuo,Ohnishi, Yasuo
, p. 6631 - 6639 (2018)
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.
Highly selective and controllable synthesis of arylhydroxylamines by the reduction of nitroarenes with an electron-withdrawing group using a new nitroreductase BaNTR1
Nguyen-Tran, Hieu-Huy,Zheng, Gao-Wei,Qian, Xu-Hong,Xu, Jian-He
supporting information, p. 2861 - 2864 (2014/03/21)
A new bacterial nitroreductase has been identified and used as a biocatalyst for the controllable reduction of a variety of nitroarenes with an electron-withdrawing group to the corresponding N-arylhydroxylamines under mild reaction conditions with excellent selectivity (>99%). This method therefore represents a green and efficient method for the synthesis of arylhydroxylamines.