Biosynthesis of pyruvic acid from glucose by Blastobotrys adeninivorans

Appl Microbiol Biotechnol. 2016 Sep;100(17):7689-97. doi: 10.1007/s00253-016-7618-1. Epub 2016 May 24.

Abstract

The ability of taxonomically different yeasts to synthesize pyruvic acid (PA) from glucose was studied. The study showed that many yeasts are able to produce PA from glucose under the condition of growth limitation by thiamine. This ability was found in the yeast Blastobotrys adeninivorans for the first time. The production (oversynthesis) of PA in this yeast can be explained by disturbance in the function of thiamine-dependent pyruvate dehydrogenase. Namely, the partial inhibition of this enzyme brings about the excretion of PA from the yeast cells. Due to incomplete inhibition of pyruvate dehydrogenase, the formation of acetyl-CoA continues, although at a lower level, maintaining the synthesis of α-ketoglutaric acid (KGA) in the tricarboxylic acid (TCA) cycle. KGA is no longer oxidized in the TCA cycle, because thiamine limitation inhibits α-ketoglutarate dehydrogenase. As a result, KGA is excreted from the yeast cells as a byproduct of PA oversynthesis. Furthermore, the increased level of KGA in the yeast cells inhibits NAD-dependent isocitrate dehydrogenase in the TCA cycle and enhances the production and excretion of citric acid, another byproduct of PA oversynthesis. During cultivation in a fermentor, the strain Blastobotrys adeninivorans VKM Y-2677 produced 43.2 g l(-1) PA from glucose with a product yield (YPA) of 0.77 g PA/g glucose. The proportion of PA to byproducts was 18:1 for KGA and 8:1 for citric acid.

Keywords: Overproduction of metabolites; Pyruvic acid (PA) production; Thiamine limitation; Yeast Blastobotrys adeninivorans; α-ketoglutaric acid (KGA) production.

MeSH terms

  • Citric Acid / metabolism
  • Glucose / metabolism
  • Ketoglutaric Acids / metabolism
  • Pyruvate Dehydrogenase Complex / metabolism*
  • Pyruvic Acid / metabolism*
  • Saccharomycetales / metabolism*
  • Thiamine / metabolism*

Substances

  • Ketoglutaric Acids
  • Pyruvate Dehydrogenase Complex
  • Citric Acid
  • Pyruvic Acid
  • Glucose
  • Thiamine