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From the
1 From the Department of Biochemistry, University of California, Berkeley, California 94720
Subcellular fractions of Mycobacterium phlei have been shown to catalyze the biosynthesis of several mannosyl derivatives of phosphatidylmyoinositol, to which we have given the generic name "mannophosphoinositides." The major products are a family of dimannophosphoinositides, three in number, and these appear to differ only in the number of fatty acyl groups they contain. Phosphatidylmyoinositol is an effective mannose acceptor and guanosine diphosphate mannose, the sugar donor in the biosynthesis of these complex phospholipids. The three dimannophosphoinositides, A, B, and C, contain, respectively, 4, 3, and 2 moles of fatty acid per phosphate residue in the molecule. Since two of the fatty acid groups are probably present in the phosphatidyl residue, dimannophosphoinositides A and B must be acylated in addition on the mannose or myoinositol parts. The origin of these additional fatty acyl groups is unknown. The enzyme activities which catalyze the biosynthesis of the mannophosphoinositides are present in both the soluble and particulate fractions of cells disrupted by sonic treatment. The particulate enzyme can be "solubilized" by acetone treatment. The various enzyme activities differ in their requirements, substrate specificities, and detergent effects in ways which are not readily explainable. The acceptor ability of phosphatidylmyoinositol from different sources and following different treatments varies widely. All of these observations probably reflect the complexity of the enzyme system which undoubtedly contains several mannosyltransferases as well as the acylating activity. As a working hypothesis, we suggest that GDP-mannose acts as the donor in the conversion of phosphatidylmyoinositol to phosphatidylmyoinositol dimannoside (dimannophosphoinositide C), and the latter is then acylated in a two-step process to yield first dimannophosphoinositide B and then dimannophosphoinositide A. Alternatively, the intermediate monomannophosphoinositide could be acylated before addition of the second mannose, leading then directly to dimannophosphoinositide B. Presumably, these substances are all precursors of the higher polymannophosphoinositides, including the pentamannoside.
Biosynthesis of Mannophosphoinositides by Mycobacterium phlei
THE FAMILY OF DIMANNOPHOSPHOINOSITIDES
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