Metabolic engineering of Saccharomyces cerevisiae for production of 3-hydroxypropionic acid

Baker's yeast Saccharomyces cerevisiae is an attractive cell factory for sustainable production of chemicals, due to its safe use status, tolerance of low pH and inhibitors, and amenability to large-scale fermentations. We engineered S. cerevisiae for production of 3-hydroxypropionic acid (3HP). 3HP can be chemically dehydrated into acrylic acid and thus serve as a biosustainable building block for acrylate-based products (diapers, acrylic paints, acrylic polymers, etc.)
We considered several biosynthetic pathways leading to 3HP, screened for efficient enzyme variants and optimized gene expression using novel synthetic biology tools that we developed for stable single and multi-copy integration of genes into yeast genome. Engineering of precursor and co-factor supply by using both rational and model-guided approaches and optimizing fermentation parameters helped to further improve 3HP titer, production rate and yield. Adaptive laboratory evolution followed by genome re-sequencing, transcriptome analysis and reverse engineering allowed to decipher 3HP tolerance mechanism.
In summary, we show how modern synthetic biology and metabolic engineering tools can be used to rapidly engineer S. cerevisiae for production of a heterologous hydroxyalkanoic acid.