J Biol Chem 2021 Apr 14:100643. Epub 2021 Apr 14.
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Morgridge Institute for Research, Madison, WI 53715, USA; National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA; Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA. Electronic address:
Coenzyme Q (CoQ), a redox-active lipid essential for oxidative phosphorylation, is synthesized by virtually all cells, but how eukaryotes make the universal CoQ head group precursor 4-hydroxybenzoate (4-HB) from tyrosine is unknown. The first and last steps of this pathway have been defined in Saccharomyces cerevisiae, but the intermediates and enzymes involved in converting 4-hydroxyphenylpyruvate (4-HPP) to 4-hydroxybenzaldehyde (4-HBz) have not been described. Here, we interrogate this pathway with genetic screens, targeted LC-MS, and chemical genetics. Read More