title: Coupled incremental precursor and co-factor supply improves 3-hydroxypropionic acid production in Saccharomyces cerevisiae.
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.
authors: Department of Chemical and Biological Engineering, Chalmers University of Technology, Kemivägen 10, SE-41296 Göteborg, Sweden.
authors: Yun
authors: Y
authors: Chen
authors: Department of Chemical and Biological Engineering, Chalmers University of Technology, Kemivägen 10, SE-41296 Göteborg, Sweden.
authors: Jichen
authors: J
authors: Bao
authors: Department of Chemical and Biological Engineering, Chalmers University of Technology, Kemivägen 10, SE-41296 Göteborg, Sweden.
authors: Il-Kwon
authors: IK
authors: Kim
authors: Department of Chemical and Biological Engineering, Chalmers University of Technology, Kemivägen 10, SE-41296 Göteborg, Sweden.
authors: Verena
authors: V
authors: Siewers
authors: Department of Chemical and Biological Engineering, Chalmers University of Technology, Kemivägen 10, SE-41296 Göteborg, Sweden. Electronic address: nielsenj@chalmers.se.
authors: Jens
authors: J
authors: Nielsen
mesh_terms: D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis; D008316:Malonyl Coenzyme A / Q000235:genetics / Q000378:metabolism*; D009249:NADP / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*
chemical_list: D019344:Lactic Acid; D008316:Malonyl Coenzyme A; D009249:NADP; C031601:hydracrylic acid
keywords: 3-hydroxypropionic acid; NADPH; Saccharomyces cerevisiae; malonyl-CoA