<?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><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%">Gardocki, Mary Elizabeth</style></author><author><style face="normal" font="default" size="100%">Lopes, John M</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Expression of the yeast PIS1 gene requires multiple regulatory elements including a Rox1p binding site.</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%">Anoxia</style></keyword><keyword><style  face="normal" font="default" size="100%">Base Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">Binding Sites</style></keyword><keyword><style  face="normal" font="default" size="100%">Carbon</style></keyword><keyword><style  face="normal" font="default" size="100%">Chloramphenicol O-Acetyltransferase</style></keyword><keyword><style  face="normal" font="default" size="100%">Choline</style></keyword><keyword><style  face="normal" font="default" size="100%">Chromatography, Thin Layer</style></keyword><keyword><style  face="normal" font="default" size="100%">Conserved Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA, Complementary</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA-Binding Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Deletion</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation, Fungal</style></keyword><keyword><style  face="normal" font="default" size="100%">Genes, Reporter</style></keyword><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%">Models, Biological</style></keyword><keyword><style  face="normal" font="default" size="100%">Models, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword><keyword><style  face="normal" font="default" size="100%">Oxygen</style></keyword><keyword><style  face="normal" font="default" size="100%">Phospholipids</style></keyword><keyword><style  face="normal" font="default" size="100%">Plasmids</style></keyword><keyword><style  face="normal" font="default" size="100%">Promoter Regions, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Binding</style></keyword><keyword><style  face="normal" font="default" size="100%">Repressor Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA</style></keyword><keyword><style  face="normal" font="default" size="100%">Saccharomyces cerevisiae</style></keyword><keyword><style  face="normal" font="default" size="100%">Saccharomyces cerevisiae Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcription, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Transferases (Other Substituted Phosphate Groups)</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2003</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2003 Oct 3</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">278</style></volume><pages><style face="normal" font="default" size="100%">38646-52</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">The PIS1 gene is required for de novo synthesis of phosphatidylinositol (PI), an essential phospholipid in Saccharomyces cerevisiae. PIS1 gene expression is unusual because it is uncoupled from the other phospholipid biosynthetic genes, which are regulated in response to inositol and choline. Relatively little is known about regulation of transcription of the PIS1 gene. We reported previously that PIS1 transcription is sensitive to carbon source. To further our understanding of the regulation of PIS1 transcription, we carried out a promoter deletion analysis that identified three regions required for PIS1 gene expression (upstream activating sequence (UAS) elements 1-3). Deletion of either UAS1 or UAS2 resulted in an approximately 45% reduction in expression, whereas removal of UAS3 yielded an 84% decrease in expression. A comparison of promoters among several Saccharomyces species shows that these sequences are highly conserved. Curiously, the UAS3 element region (-149 to -138) includes a Rox1p binding site. Rox1p is a repressor of hypoxic genes under aerobic growth conditions. Consistent with this, we have found that expression of a PIS1-cat reporter was repressed under aerobic conditions, and this repression was dependent on both Rox1p and its binding site. Furthermore, PI levels were elevated under anaerobic conditions. This is the first evidence that PI levels are affected by regulation of PIS1 transcription.</style></abstract><issue><style face="normal" font="default" size="100%">40</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/12890676?dopt=Abstract</style></custom1></record></records></xml>