Tuesday, May 6, 2008 - 9:00 AM
7-03
Metabolic Engineering of Saccharomyces cerevisiae for Succinic Acid Production
José Manuel Otero, Simon G Poulsen, Jens Nielsen, and Lisbeth Olsson. Center for Microbial Biotechnology, BioCentrum-DTU, Building 223, Lyngby, Denmark
A class of high added-value chemicals being targeted for biotechnology production is C4 organic acids, encompassing fumaric, malic, and succinic acid. Succinic acid is a key building block molecule for further conversion to precursor molecules such as tetrahydrofuran, 1,4-butanediol, and butyrolactone. Succinic acid has the potential to become a commodity chemical, with world-wide annual demand exceeding $2 billion USD and over 160 million kilograms currently produced from petrochemical conversion of maleic anhydride. There are several biomass platforms, all prokaryotic, for succinic acid production; however, overproduction of succinic acid in S. cerevisiae offers distinct process advantages. For example, S. cerevisiae has been awarded GRAS status, grows well at low pH significantly minimizing purification costs, and can utilize diverse carbon substrates in chemically defined medium. Furthermore, Saccharomyces cerevisiae is a proven, robust, industrial production platform.
S. cerevisiae offers the unique advantage of being the most well characterized eukaryotic expression system. Here we describe the use of systems biology tools to drive C6 carbon flux to succinic acid by enhancement of the two native pathways for succinic acid production: the TCA and glyoxylate cycles. S. cerevisiae do naturally only accumulate succinic acid in minor amounts; 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 and we can show a 70-fold overproduction compared to the natural level of succinic acid produced. Metabolic engineering approaches developed promise to have broad applicability to industrial biotechnology platforms.
S. cerevisiae offers the unique advantage of being the most well characterized eukaryotic expression system. Here we describe the use of systems biology tools to drive C6 carbon flux to succinic acid by enhancement of the two native pathways for succinic acid production: the TCA and glyoxylate cycles. S. cerevisiae do naturally only accumulate succinic acid in minor amounts; 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 and we can show a 70-fold overproduction compared to the natural level of succinic acid produced. Metabolic engineering approaches developed promise to have broad applicability to industrial biotechnology platforms.
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See more of The 30th Symposium on Biotechnology for Fuels and Chemicals (May 4 -- 7, 2008)