Inhibition of eukaryotic DNA polymerase alpha with a novel lysophosphatidic acid (PHYLPA) isolated from myxoamoebae of Physarum polycephalum

J Biol Chem. 1992 Oct 25;267(30):21512-7.


A specific inhibitor of DNA polymerase alpha was isolated from the lipid fraction prepared from myxoamoebae of a true slime mold, Physarum polycephalum. The purified substance was subjected to structural studies by fast atom bombardment mass spectroscopy, infrared spectroscopy, and two-dimensional nuclear magnetic resonance spectroscopy. The structure of this substance was thereby suggested to be a novel lysophosphatidic acid (LPA) composed of cyclic phosphate and cyclopropane-containing hexadecanoic acid. Then we named this substance PHYLPA (Physarum LPA). PHYLPA inhibited more than 80% of the affinity-purified calf thymus DNA polymerase alpha activity at a concentration of 10 micrograms/ml (approximately 20 microM). Inhibition was observed for DNA polymerase alpha but not for DNA polymerase beta or gamma from various eukaryotic species, nor did it inhibit DNA polymerase I from E. coli. From kinetic analyses, the inhibition was considered to be caused by the interaction of PHYLPA with the template DNA.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • DNA Polymerase II / antagonists & inhibitors*
  • DNA, Fungal / biosynthesis
  • Lysophospholipids / chemistry
  • Lysophospholipids / isolation & purification
  • Lysophospholipids / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Physarum polycephalum / chemistry
  • Physarum polycephalum / enzymology*
  • Spectrometry, Mass, Fast Atom Bombardment
  • Spectrophotometry, Infrared


  • DNA, Fungal
  • Lysophospholipids
  • DNA Polymerase II