Chitin synthase

Fungal chitin synthases are found as integral proteins of the plasma membrane and in chitosomes a divalent cation, Mg(II), is necessary for enzyme activity but neither primers nor a hpid intermediate are required. The substrate and free GlcNAc activate the allosteric enzyme. UDP, the byproduct of the enzymatic activity, is strongly inhibitory to chitin synthase however, it may be metabohzed readily to UMP by a diphosphatase. 

Inhibition of chitin synthase II Effect against enzyme-dependent and enzyme-independent lipid peroxydation... 

Mueller C, Hansen K, Szabo P, Nielsen J. (2003) Effect of deletion of chitin synthase genes on mycelial morphology and culture viscosity in Aspergillus oryzae. Biotechnol Bioeng 81 525-534. 

Both compounds (Figure 4.7) are non-competitive inhibitors of chitin synthase and also interfere with the Bremner-Greenberg methylation pathway.6 Their activity is dependent upon the oxidation of the phosphorous - sulfur linkage, a feature that is the basis of resistance development, which is common sensitive strains of P. oryzae metabolise the compounds more rapidly than resistant strains. 

Chitin synthase is localised in the plasma membrane at the apex of... 

Chitin. Like cellulose synthase, fungal chitin synthases are present in the plasma membrane and extrude microfibrils of chitin to the outside.147 150 In the fungus Mucor the majority of the chitin synthesized later has its N-acetyl groups removed hydrolytically to form the deacetylated polymer chitosan.151152 Chitin is also a major component of insect exoskeletons. For this reason, chitin synthase is an appropriate target enzyme for design of synthetic insecticides.153... 

The reaction is catalyzed by a single enzyme, namely, UDP-2-acetamido-2-deoxy-D-glucose chitin 2-acetamido-2-deoxy-D-glucosyltransferase (chitin synthase, EC 2.4.1.16). Particulate preparations of chitin synthase obtained from different fungi211 did not show significant differences. The enzyme exists in the cells as inactive zymogen, and can be converted into the active form by limited proteolysis.212 The zymogenic character of chitin synthase was also confirmed in solubilized preparations,213,214 as well as in preparations from other sources.211... 

Perhaps the most remarkable property of fungal, chitin synthase is that the presence of an endogenous primer is not absolutely necessary for the reaction to proceed. Solubilized preparations of chitin synthase are able to synthesize chitin with no macromolecular primer present.210,213"215 This property is difficult to understand when chitin synthase is compared with other glycosyltransferases. On the other hand, crustacean chitin synthase incorporates 2-acetamido-2-deoxy-D-glucose into an endogenous acceptor... 

Pfefferle W, Anke H, Bross M, Steglich W (1990) Inhibition of Solubilized Chitin Synthase by Chlorinated Aromatic Compounds Isolated from Mushroom Cultures. Agric Biol Chem 54 1381... 

Another group of fungicides interferes with cell wall formation. Two examples of this group include 1) the polyoxines, which prevent chitin formation by competitively inhibiting chitin-synthase, the final enzyme involved in chitin biosynthesis, and 2) melanine biosynthesis inhibitors, especially in Pyricularia oryzae. Examples of... 

The parallels among chitin, cellulose, and HA structures, all being j3 -chains of hexose polymers are reflected in the striking similarity in sequence between the HAS from vertebrates, cellulose synthases from plants, and chitin synthases from fungi. A primordial ancestral gene must have existed from which all of these enzymes evolved that are involved in the biosynthesis of all polymers that contain -glycoside linkages, an ancient j3-polysaccharide synthase. 

Triflumuron (Alsystin , Baycidal ) [91,92], an /V-benzoyl-W-phenyl urea chitin synthase inhibitor commercialized by Bayer CropScience, is a broad spectrum insecticide that is active against chewing insects, as well as fleas and cockroaches. 

Chitin synthase inhibitors are used commercially as insecticides because they preventthe formation of a new exoskeleton and the shedding of the old one. The insect becomes trapped in an old exoskeleton that cannot grow. These inhibitors are highly toxic to insects and crustaceans, but relatively nontoxic to mammals. The most common chitin synthase inhibitors are substituted benzoyl-ureas such as diflubenzuron, which was first registered as an insecticide in 1976. 

Diflubenzuron inhibits the enzyme chitin synthase, which is required in the final step of chitin synthesis. Chitin is a polysaccharide and a major constituent of the exoskeleton of insects. In insects, the trachea is held open by rings of chitin. The exoskeleton and waxy covering also prevent water loss. Inhibiting chitin synthesis therefore can provide an effective means of pest control. Moreover, vertebrates and most plants do not utilize chitin, thus making diflubenzuron a target-selective pesticide. 

Some anti-frmgal agents such as tricyclazole produce a weakening of cell walls by inhibiting melanin biosynthesis. More recently, several compounds that target the p-(l,3)-D-glucan and chitin synthases have been developed. 

UDP-glucosamine — the substrate for chitin synthase, drawn to show its similarity to polyoxin B... 

Nikkomycins are nucleoside amide antibiotics produced by Streptomyces tendae Tii 901 and are known to show antifungal, anti-insecticidal, and acaricidal activities. They are competitive inhibitors of chitin synthase. Nikkomycins are produced as a complex mixture, with nikkomycin Z (13) and nikkomycin X (14) representing the major components. ... 

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