Reconstruction of cytosolic fumaric acid biosynthetic pathways in Saccharomyces cerevisiae

Abstract

<p>Abstract</p> <p>Background</p> <p>Fumaric acid is a commercially important component of foodstuffs, pharmaceuticals and industrial materials, yet the current methods of production are unsustainable and ecologically destructive.</p> <p>Results</p> <p>In this study, the fumarate biosynthetic pathway involving reductive reactions of the tricarboxylic acid cycle was exogenously introduced in <it>S. cerevisiae </it>by a series of simple genetic modifications. First, the <it>Rhizopus oryzae </it>genes for malate dehydrogenase (<it>RoMDH</it>) and fumarase (<it>RoFUM1</it>) were heterologously expressed. Then, expression of the endogenous pyruvate carboxylase (<it>PYC2</it>) was up-regulated. The resultant yeast strain, FMME-001 ↑<it>PYC2 </it>+ ↑<it>RoMDH</it>, was capable of producing significantly higher yields of fumarate in the glucose medium (3.18 ± 0.15 g liter<sup>-1</sup>) than the control strain FMME-001 empty vector.</p> <p>Conclusions</p> <p>The results presented here provide a novel strategy for fumarate biosynthesis, which represents an important advancement in producing high yields of fumarate in a sustainable and ecologically-friendly manner.</p

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