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Genetic Engineering of an Unconventional Yeast for Renewable Biofuel and Biochemical Production
10:10

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Published on: September 20, 2016

Riboneogenesis in yeast.

Michelle F Clasquin1, Eugene Melamud, Alexander Singer

  • 1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton NJ 08544, USA.

Cell
|June 14, 2011
PubMed
Summary
This summary is machine-generated.

Yeast utilize riboneogenesis to create ribose-5-phosphate from glycolysis intermediates. This new pathway, identified by the enzyme sedoheptulose-1,7-bisphosphatase (SHB17), bypasses NADPH production.

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Area of Science:

  • Metabolic pathways
  • Biochemistry
  • Yeast metabolism

Background:

  • Glucose catabolism in yeast occurs via glycolysis and the oxidative pentose phosphate pathway (PPP).
  • The oxidative PPP produces NADPH and ribose-5-phosphate, crucial for nucleotide synthesis.
  • Existing pathways do not efficiently produce ribose-5-phosphate independently of NADPH.

Purpose of the Study:

  • To identify and characterize a novel metabolic pathway for ribose-5-phosphate synthesis in yeast.
  • To elucidate the enzymatic steps and regulation of this new pathway, termed riboneogenesis.
  • To understand the conditions under which riboneogenesis is favored over NADPH production.

Main Methods:

  • Metabolomic analysis of yeast knockout strains.
  • Enzyme activity assays.
  • Crystal structure determination of sedoheptulose-1,7-bisphosphatase (SHB17).

Main Results:

  • Discovery of riboneogenesis, a pathway converting glycolytic intermediates to ribose-5-phosphate without NADPH production.
  • Identification of sedoheptulose-1,7-bisphosphatase (SHB17) as the key enzyme in the committed step.
  • Structural analysis of SHB17 bound to its substrate, sedoheptulose-1,7-bisphosphate.
  • Demonstration that SHB17 flux increases with high ribose demand, such as during ribosome biogenesis.

Conclusions:

  • Riboneogenesis represents a distinct route for ribose-5-phosphate synthesis in yeast.
  • SHB17 is a critical enzyme that commits sedoheptulose-1,7-bisphosphate to riboneogenesis.
  • This pathway's activity is regulated by the relative demand for ribose versus NADPH.