Coupled incremental precursor and co-factor supply improves 3-hydroxypropionic acid production in Saccharomyces cerevisiae |
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| Affiliation: | 1. Department of Biochemistry & Molecular Biology, University of Georgia, Athens, GA 30602, United States;2. Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27695, United States;1. Interdisciplinary Program of Bioengineering, Seoul National University, Seoul 151-921, South Korea;2. Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, South Korea;3. Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, South Korea;1. Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 08826, Republic of Korea;2. Interdisciplinary Program of Bioengineering, Seoul National University, Seoul 08826, Republic of Korea;3. Department of Biotechnology, Graduate School, Korea University, Seoul 02841, Republic of Korea;4. Graduate School of International Agricultural Technology, Seoul National University, Pyeongchang 25354, Republic of Korea;5. Institutes of Green Bio Science and Technology, Seoul National University, Pyeongchang 25354, Republic of Korea;1. Institute of Applied Chemistry, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China;2. Tsinghua Innovation Center in Dongguan, Dongguan 523808, China |
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| Abstract: | 3-Hydroxypropionic acid (3-HP) is an attractive platform chemical, which can be used to produce a variety of commodity chemicals, such as acrylic acid and acrylamide. For enabling a sustainable alternative to petrochemicals as the feedstock for these commercially important chemicals, fermentative production of 3-HP is widely investigated and is centered on bacterial systems in most cases. However, bacteria present certain drawbacks for large-scale organic acid production. In this study, we have evaluated the production of 3-HP in the budding yeast Saccharomyces cerevisiae through a route from malonyl-CoA, because this allows performing the fermentation at low pH thus making the overall process cheaper. We have further engineered the host strain by increasing availability of the precursor malonyl-CoA and by coupling the production with increased NADPH supply we were able to substantially improve 3-HP production by five-fold, up to a final titer of 463 mg l−1. Our work thus led to a demonstration of 3-HP production in yeast via the malonyl-CoA pathway, and this opens for the use of yeast as a cell factory for production of bio-based 3-HP and derived acrylates in the future. |
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| Keywords: | 3-hydroxypropionic acid malonyl-CoA NADPH |
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