Identification of apolipoprotein N-acyltransferase (Lnt) in mycobacteria

J Biol Chem. 2009 Oct 2;284(40):27146-56. doi: 10.1074/jbc.M109.022715. Epub 2009 Aug 6.

Abstract

Lipoproteins of Gram-negative and Gram-positive bacteria carry a thioether-bound diacylglycerol but differ by a fatty acid amide bound to the alpha-amino group of the universally conserved cysteine. In Escherichia coli the N-terminal acylation is catalyzed by the N-acyltransferase Lnt. Using E. coli Lnt as a query in a BLASTp search, we identified putative lnt genes also in Gram-positive mycobacteria. The Mycobacterium tuberculosis lipoprotein LppX, heterologously expressed in Mycobacterium smegmatis, was N-acylated at the N-terminal cysteine, whereas LppX expressed in a M. smegmatis lnt::aph knock-out mutant was accessible for N-terminal sequencing. Western blot analyses of a truncated and tagged form of LppX indicated a smaller size of about 0.3 kDa in the lnt::aph mutant compared with the parental strain. Matrix-assisted laser desorption ionization time-of-flight/time-of-flight analyses of a trypsin digest of LppX proved the presence of the diacylglycerol modification in both strains, the parental strain and lnt::aph mutant. N-Acylation was found exclusively in the M. smegmatis parental strain. Complementation of the lnt::aph mutant with M. tuberculosis ppm1 restored N-acylation. The substrate for N-acylation is a C16 fatty acid, whereas the two fatty acids of the diacylglycerol residue were identified as C16 and C19:0 fatty acid, the latter most likely tuberculostearic acid. We demonstrate that mycobacterial lipoproteins are triacylated. For the first time to our knowledge, we identify Lnt activity in Gram-positive bacteria and assigned the responsible genes. In M. smegmatis and M. tuberculosis the open reading frames are annotated as MSMEG_3860 and M. tuberculosis ppm1, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinobacteria / enzymology
  • Acylation
  • Acyltransferases / chemistry
  • Acyltransferases / genetics
  • Acyltransferases / metabolism*
  • Amino Acid Sequence
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Fatty Acids / metabolism
  • Genome, Bacterial
  • Lipoproteins / metabolism
  • Molecular Sequence Data
  • Mutation
  • Mycobacterium / enzymology*
  • Mycobacterium / genetics
  • Sequence Homology, Amino Acid
  • Species Specificity

Substances

  • Fatty Acids
  • Lipoproteins
  • Acyltransferases
  • apolipoprotein N-acyltransferase