Metabolic engineering of Saccharomyces cerevisiae for the biotechnological production of succinic acid |
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| Authors: | Andreas M Raab Gabi Gebhardt Natalia Bolotina Dirk Weuster-Botz Christine Lang |
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| Institution: | 1. Berlin University of Technology, Institute for Biotechnology, Department of Microbiology and Genetics, Gustav-Meyer-Allee 25, D-13355 Berlin, Germany;2. ORGANOBALANCE GmbH, Gustav-Meyer-Allee 25, D-13355 Berlin, Germany;3. Technische Universität München, Institute of Biochemical Engineering, Boltzmannstr. 15, D-85748 Garching, Germany;1. Department of Chemical and Biomolecular Engineering, Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States;2. Departments of Chemistry, Biochemistry, and Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States;1. College of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044, China;2. College of Bioengineering, Chongqing University, Chongqing 400044, China;1. Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, Guangdong 518120, People’s Republic of China;2. School of Energy and Environment, City University of Hong Kong, Hong Kong;3. School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, People’s Republic of China;1. School of Energy and Environment, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China;2. Microbial Processes and Interactions, TERRA Teaching and Research Center, University of Liège – Gembloux Agro-Bio Tech, Av. De la Faculté, 2B, 5030 Gembloux, Belgium;1. Laboratory of Food Chemistry and Biochemistry, Leuven Food Science and Nutrition Research Centre (LFoRCe) KU Leuven, Kasteelpark Arenberg 20 – Box 2463, B-3001 Leuven, Belgium;2. VIB Laboratory for Systems Biology & CMPG Laboratory for Genetics and Genomics, KU Leuven, Bio-Incubator, Gaston Geenslaan 1, B-3001 Leuven, Belgium;1. State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, Jiangsu 211800, China;2. Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, Nanjing, Jiangsu 211800, China;3. Renewable and Sustainable Energy Institute (RASEI), University of Colorado Boulder, 4001 Discovery Dr. Suite N321, Boulder 80309, USA |
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| Abstract: | The production of bio-based succinic acid is receiving great attention, and several predominantly prokaryotic organisms have been evaluated for this purpose. In this study we report on the suitability of the highly acid- and osmotolerant yeast Saccharomyces cerevisiae as a succinic acid production host. We implemented a metabolic engineering strategy for the oxidative production of succinic acid in yeast by deletion of the genes SDH1, SDH2, IDH1 and IDP1. The engineered strains harbor a TCA cycle that is completely interrupted after the intermediates isocitrate and succinate. The strains show no serious growth constraints on glucose. In glucose-grown shake flask cultures, the quadruple deletion strain Δsdh1Δsdh2Δidh1Δidp1 produces succinic acid at a titer of 3.62 g L?1 (factor 4.8 compared to wild-type) at a yield of 0.11 mol (mol glucose)?1. Succinic acid is not accumulated intracellularly. This makes the yeast S. cerevisiae a suitable and promising candidate for the biotechnological production of succinic acid on an industrial scale. |
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