title: Inositol lipid metabolism in mycobacteria: biosynthesis and regulatory mechanisms.
abstract: 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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. ymorita@biken.osaka-u.ac.jp
authors.forename: Yasu S
authors.initials: YS
authors.lastname: Morita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukuda
authors.forename: Chubert B C
authors.initials: CB
authors.lastname: Sena
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamaryo-Botte
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: McConville
authors.forename: Taroh
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: D007294:Inositol / Q000737:chemistry / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology*; D008055:Lipids / Q000737:chemistry; D008954:Models, Biological; D009161:Mycobacterium / Q000737:chemistry / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000737:chemistry / Q000378:metabolism
chemical_list: D008055:Lipids; D010716:Phosphatidylinositols; D007294:Inositol