Coupled incremental precursor and co-factor supply improves 3-hydroxypropionic acid production in Saccharomyces cerevisiae

Chen, Yun,1978Chalmers tekniska högskola,Chalmers University of Technology (author)

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. (C) 2014 International Metabolic Engineering Society.

Bao, Jichen,1988Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)jichen (author)
Kim, Il-Kwon,1969Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)ilkwon (author)
Siewers, Verena,1976Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)siewers (author)
Nielsen, Jens B,1962Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)nielsenj (author)
Chalmers tekniska högskola (creator_code:org_t)

By the author/editor: Chen, Yun, 1978; Bao, Jichen, 198 ...; Kim, Il-Kwon, 19 ...; Siewers, Verena, ...; Nielsen, Jens B, ...

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