title: An Adaptation To Life In Acid Through A Novel Mevalonate Pathway.
abstract: Extreme acidophiles are capable of growth at pH values near zero. Sustaining life in acidic environments requires extensive adaptations of membranes, proton pumps, and DNA repair mechanisms. Here we describe an adaptation of a core biochemical pathway, the mevalonate pathway, in extreme acidophiles. Two previously known mevalonate pathways involve ATP dependent decarboxylation of either mevalonate 5-phosphate or mevalonate 5-pyrophosphate, in which a single enzyme carries out two essential steps: (1) phosphorylation of the mevalonate moiety at the 3-OH position and (2) subsequent decarboxylation. We now demonstrate that in extreme acidophiles, decarboxylation is carried out by two separate steps: previously identified enzymes generate mevalonate 3,5-bisphosphate and a new decarboxylase we describe here, mevalonate 3,5-bisphosphate decarboxylase, produces isopentenyl phosphate. Why use two enzymes in acidophiles when one enzyme provides both functionalities in all other organisms examined to date? We find that at low pH, the dual function enzyme, mevalonate 5-phosphate decarboxylase is unable to carry out the first phosphorylation step, yet retains its ability to perform decarboxylation. We therefore propose that extreme acidophiles had to replace the dual-purpose enzyme with two specialized enzymes to efficiently produce isoprenoids in extremely acidic environments.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Vinokur
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Cummins
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095, USA.
authors.forename: Tyler P
authors.initials: TP
authors.lastname: Korman
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095, USA.
authors.forename: James U
authors.initials: JU
authors.lastname: Bowie
mesh_terms: D000220:Adaptation, Biological / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D008798:Mevalonic Acid / Q000378:metabolism*; D013822:Thermoplasma / Q000235:genetics / Q000378:metabolism*
chemical_list: D008798:Mevalonic Acid