<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Morita, Yasu S</style></author><author><style face="normal" font="default" size="100%">Fukuda, Takeshi</style></author><author><style face="normal" font="default" size="100%">Sena, Chubert B C</style></author><author><style face="normal" font="default" size="100%">Yamaryo-Botte, Yoshiki</style></author><author><style face="normal" font="default" size="100%">McConville, Malcolm J</style></author><author><style face="normal" font="default" size="100%">Kinoshita, Taroh</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Inositol lipid metabolism in mycobacteria: biosynthesis and regulatory mechanisms.</style></title><secondary-title><style face="normal" font="default" size="100%">Biochim Biophys Acta</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Biochim. Biophys. Acta</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Inositol</style></keyword><keyword><style  face="normal" font="default" size="100%">Lipid Metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Lipids</style></keyword><keyword><style  face="normal" font="default" size="100%">Models, Biological</style></keyword><keyword><style  face="normal" font="default" size="100%">Mycobacterium</style></keyword><keyword><style  face="normal" font="default" size="100%">Phosphatidylinositols</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2011 Jun</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">1810</style></volume><pages><style face="normal" font="default" size="100%">630-41</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">BACKGROUND: The genus Mycobacterium includes a number of medically important pathogens. The cell walls of these bacteria have many unique features, including the abundance of various inositol lipids, such as phosphatidylinositol mannosides (PIMs), lipomannan (LM), and lipoarabinomannan (LAM). The biosynthesis of these lipids is believed to be prime drug targets, and has been clarified in detail over the past several years.

SCOPE OF REVIEW: Here we summarize our current understanding of the inositol lipid metabolism in mycobacteria. We will highlight unsolved issues and future directions especially in the context of metabolic regulation.

MAJOR CONCLUSIONS: Inositol is a building block of phosphatidylinositol (PI), which is further elaborated to become PIMs, LM and LAM. d-myo-inositol 3-phosphate is an intermediate of the de novo inositol synthesis, but it is also the starting substrate for mycothiol synthesis. Controlling the level of d-myo-inositol 3-phosphate appears to be important for maintaining the steady state levels of mycothiol and inositol lipids. Several additional control mechanisms must exist to control the complex biosynthetic pathways of PI, PIMs, LM and LAM. These may include regulatory proteins such as a lipoprotein LpqW, and spatial separation of enzymes, such as the amphipathic PimA mannosyltransferase and later enzymes in the PIMs/LM biosynthetic pathway. Finally, we discuss mechanisms that underlie control of LM/LAM glycan polymer elongation.

GENERAL SIGNIFICANCE: Mycobacteria have evolved a complex network of inositol metabolism. Clarifying its metabolism will not only provide better understanding of bacterial pathogenesis, but also understanding of the evolution and general functions of inositol lipids in nature.</style></abstract><issue><style face="normal" font="default" size="100%">6</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/21477636?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Morita, Yasu S</style></author><author><style face="normal" font="default" size="100%">Velasquez, René</style></author><author><style face="normal" font="default" size="100%">Taig, Ellen</style></author><author><style face="normal" font="default" size="100%">Waller, Ross F</style></author><author><style face="normal" font="default" size="100%">Patterson, John H</style></author><author><style face="normal" font="default" size="100%">Tull, Dedreia</style></author><author><style face="normal" font="default" size="100%">Williams, Spencer J</style></author><author><style face="normal" font="default" size="100%">Billman-Jacobe, Helen</style></author><author><style face="normal" font="default" size="100%">McConville, Malcolm J</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Compartmentalization of lipid biosynthesis in mycobacteria.</style></title><secondary-title><style face="normal" font="default" size="100%">J Biol Chem</style></secondary-title><alt-title><style face="normal" font="default" size="100%">J. Biol. Chem.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Bacterial Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Biochemistry</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Membrane</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Wall</style></keyword><keyword><style  face="normal" font="default" size="100%">Hemagglutinins</style></keyword><keyword><style  face="normal" font="default" size="100%">Lipid Metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Lipids</style></keyword><keyword><style  face="normal" font="default" size="100%">Mannosides</style></keyword><keyword><style  face="normal" font="default" size="100%">Mannosyltransferases</style></keyword><keyword><style  face="normal" font="default" size="100%">Microscopy, Electron</style></keyword><keyword><style  face="normal" font="default" size="100%">Models, Biological</style></keyword><keyword><style  face="normal" font="default" size="100%">Mycobacterium smegmatis</style></keyword><keyword><style  face="normal" font="default" size="100%">Phosphatidylethanolamines</style></keyword><keyword><style  face="normal" font="default" size="100%">Phosphatidylinositols</style></keyword><keyword><style  face="normal" font="default" size="100%">Phospholipids</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Structure, Tertiary</style></keyword><keyword><style  face="normal" font="default" size="100%">Subcellular Fractions</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2005</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2005 Jun 3</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">280</style></volume><pages><style face="normal" font="default" size="100%">21645-52</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">The plasma membrane of Mycobacterium sp. is the site of synthesis of several distinct classes of lipids that are either retained in the membrane or exported to the overlying cell envelope. Here, we provide evidence that enzymes involved in the biosynthesis of two major lipid classes, the phosphatidylinositol mannosides (PIMs) and aminophospholipids, are compartmentalized within the plasma membrane. Enzymes involved in the synthesis of early PIM intermediates were localized to a membrane subdomain termed PMf, that was clearly resolved from the cell wall by isopyknic density centrifugation and amplified in rapidly dividing Mycobacterium smegmatis. In contrast, the major pool of apolar PIMs and enzymes involved in polar PIM biosynthesis were localized to a denser fraction that contained both plasma membrane and cell wall markers (PM-CW). Based on the resistance of the PIMs to solvent extraction in live but not lysed cells, we propose that polar PIM biosynthesis occurs in the plasma membrane rather than the cell wall component of the PM-CW. Enzymes involved in phosphatidylethanolamine biosynthesis also displayed a highly polarized distribution between the PMf and PM-CW fractions. The PMf was greatly reduced in non-dividing cells, concomitant with a reduction in the synthesis and steady-state levels of PIMs and amino-phospholipids and the redistribution of PMf marker enzymes to non-PM-CW fractions. The formation of the PMf and recruitment of enzymes to this domain may thus play a role in regulating growth-specific changes in the biosynthesis of membrane and cell wall lipids.</style></abstract><issue><style face="normal" font="default" size="100%">22</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/15805104?dopt=Abstract</style></custom1></record></records></xml>