An Adaptation To Life In Acid Through A Novel Mevalonate Pathway.

Jeffrey M Vinokur,Tyler P Korman,Matthew C Cummins,James U Bowie

doi:10.1038/srep39737

Jeffrey M Vinokur, Tyler P Korman + Show 2 more

Open Access

https://doi.org/10.1038/srep39737

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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.

Highlights

Extremophiles are organisms capable of surviving in the harshest conditions on earth such as temperatures exceeding 120 °C in hydrothermal vents, salinity exceeding 5 M NaCl in evaporating lakes, and acidity below pH 0 in acid mine drainage[1,2,3]
We find that the dual function mevalonate 5-phosphate decarboxylase (MMD) from Roseiflexus castenholzii is unable to carry out the kinase step at low pH, but retains decarboxylase activity
A structural homology model of Ta0893 made with PHYRE2 suggested significant similarity to mevalonate 5-pyrophosphate decarboxylase from yeast (PDB: 1FI4, confidence score of 100%) and contained the invariant Asp/Lys/Arg catalytic triad necessary for decarboxylation in the correct positions (Fig. 3)[19,20,21]

Summary

Introduction

Extremophiles are organisms capable of surviving in the harshest conditions on earth such as temperatures exceeding 120 °C in hydrothermal vents, salinity exceeding 5 M NaCl in evaporating lakes, and acidity below pH 0 in acid mine drainage[1,2,3]. We report the identification of MBD from T. acidophilum, which produces IP through the ATP independent decarboxylation of mevalonate 3,5-bisphosphate (Fig. 2, reaction in brackets). We find that the dual function mevalonate 5-phosphate decarboxylase (MMD) from Roseiflexus castenholzii is unable to carry out the kinase step at low pH, but retains decarboxylase activity.

Results

Conclusion