Sustainable biosynthesis of 3-hydroxypropionic acid from crude glycerol: Metabolic engineering and process optimization

To achieve carbon neutrality and carbon peaking goals, biomanufacturing of high-value chemicals from sustainable biorefinery has emerged as an attractive alternative to traditional petrochemical-based processes. 3-Hydroxypropionic acid (3-HP) is one of the top value-added building-block chemicals with diverse applications, which has increased its demand for large-scale industrial production. Nevertheless, sustainable biosynthesis of 3-HP is limited by the lack of robust strains and the need for expensive fermentation medium components. Herein, efforts were made to overcome these limitations through metabolic engineering of Escherichia coli and process optimization. First, the functional 3-HP biosynthetic pathway was recruited and optimized in E. coli . Next, the endogenous glycerol facilitator (GlpF) was overexpressed to enhance glycerol uptake, and the expression level of aldehyde dehydrogenase (YdcW) was optimized for speeding up 3-HP biosynthesis. Subsequently, global regulator engineering further improved 3-HP production. Additionally, corn steep liquor (CSL) was used to develop a cheap fermentation medium. Finally, co-fermentation of crude glycerol with glucose and acetic acid using the final strain produced 67.62 g/L 3-HP with a yield and a productivity of 0.86 mol/mol glycerol and 1.41 g/L/h, respectively.