A class of added-value chemicals being targeted for biotechnology production is C₄ organic acids. Succinic acid is a key building block molecule for further conversion to precursors such as tetrahydrofuran, 1,4-butanediol, and butyrolactone. Succinic acid has the potential to become a commodity chemical, with global demand presently exceeding $2 billion USD/year, and over 160 million kilograms/year petrochemically produced. There are several biomass platforms, all prokaryotic, for succinic acid production; however, S. cerevisiae offers distinct advantages.  It has been awarded GRAS status for use in human consumables, grows well at low pH significantly minimizing purification and acidification costs, and can utilize diverse feedstocks.

Here we describe the use of systems biology tools to drive C₆ carbon flux to succinic acid by enhancement of the two native succinic acid producing pathways: the TCA and glyoxylate cycles.  S. cerevisiae does not naturally accumulate succinic acid; however, through the use of in silico metabolic predictions guiding targeted gene deletions and over-expression, mutants that overproduce succinic acid have been engineered and thoroughly characterised.