Fungal beta(1,3)-D-glucan synthesis.
The polysaccharide beta(1,3)-D-glucan is a component of the cell wall of many fungi. Synthesis of the linear polymer is catalysed by UDP-glucose beta(1,3)-D-glucan beta(3)-D-glucosyltransferase. Because this enzyme has a key role in fungal cell-wall synthesis, and because many organisms that are responsible for human mycoses, including Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, produce walls that are rich in beta(1,3)-glucan, it has been and remains the focus of intensive study. From early characterization of the enzymatic activity in Saccharomyces cerevisiae, advances have been made in purification of the enzyme, identification of essential subunits and description of regulatory circuitry that controls expression and localization of different components of the multisubunit enzyme complex. Progress in each of these areas has been enhanced dramatically by the availability of specific inhibitors of the enzymatic reaction that produces beta(1,3)-glucan. These natural product inhibitors have utility both as tools to dissect the biology of beta(1,3)-glucan synthase and as sources for development of semisynthetic derivatives with clinical utility in treatment of human fungal disease. This review will focus on the biochemistry, genetics and regulation of the enzyme.
Douglas
C M
CM
Department of Human and Animal Infectious Diseases, Merck & Co., Rahway, New Jersey 07065, USA. cameron_douglas@merck.com
D054714:Echinocandins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005658:Fungi / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005936:Glucans / Q000096:biosynthesis*; D005964:Glucosyltransferases; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D047071:beta-Glucans
D054714:Echinocandins; D005656:Fungal Proteins; D005936:Glucans; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D047071:beta-Glucans; C033363:beta-1,3-glucan; D005964:Glucosyltransferases; C091618:FKS1 protein, S cerevisiae