<?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%">Haites, Ruth E</style></author><author><style face="normal" font="default" size="100%">Morita, Yasu S</style></author><author><style face="normal" font="default" size="100%">McConville, Malcolm J</style></author><author><style face="normal" font="default" size="100%">Billman-Jacobe, Helen</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Function of phosphatidylinositol 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%">Inositol</style></keyword><keyword><style  face="normal" font="default" size="100%">Lipopolysaccharides</style></keyword><keyword><style  face="normal" font="default" size="100%">Mannose</style></keyword><keyword><style  face="normal" font="default" size="100%">Mycobacterium smegmatis</style></keyword><keyword><style  face="normal" font="default" size="100%">Phosphatidylinositols</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 Mar 25</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">280</style></volume><pages><style face="normal" font="default" size="100%">10981-7</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Phosphatidylinositol (PI) is an abundant phospholipid in the cytoplasmic membrane of mycobacteria and the precursor for more complex glycolipids, such as the PI mannosides (PIMs) and lipoarabinomannan (LAM). To investigate whether the large steady-state pools of PI and apolar PIMs are required for mycobacterial growth, we have generated a Mycobacterium smegmatis inositol auxotroph by disruption of the ino1 gene. The ino1 mutant displayed wild-type growth rates and steady-state levels of PI, PIM, and LAM when grown in the presence of 1 mM inositol. The non-dividing ino1 mutant was highly resistant to inositol starvation, reflecting the slow turnover of inositol lipids in this stage. In contrast, dilution of growing or stationary-phase ino1 mutant in inositol-free medium resulted in the rapid depletion of PI and apolar PIMs. Whereas depletion of these lipids was not associated with loss of viability, subsequent depletion of polar PIMs coincided with loss of major cell wall components and cell viability. Metabolic labeling experiments confirmed that the large pools of PI and apolar PIMs were used to sustain polar PIM and LAM biosynthesis during inositol limitation. They also showed that under non-limiting conditions, PI is catabolized via lyso-PI. These data suggest that large pools of PI and apolar PIMs are not essential for membrane integrity but are required to sustain polar PIM biosynthesis, which is essential for mycobacterial growth.</style></abstract><issue><style face="normal" font="default" size="100%">12</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/15634688?dopt=Abstract</style></custom1></record></records></xml>