Dual synthetic pathway for 3-hydroxypropionic acid production in engineered Escherichia coli

Abstract

3-Hydroxypropionic acid (3-HP) is an important platform C3 chemical; production of 3-HP in recombinant Escherichia coli by synthetic pathways has been the focus of a lot of research. When glycerol is used as a substrate to produce 3-HP in E. coli, only the ALDH pathway (employing aldehyde dehydrogenase (ALDH) for conversion of 3-hydroxypropionaldehyde (3-HPA) into 3-HP) has been utilized as a synthetic pathway. However, several bacteria (including Klebsiella pneumoniae) are known to have the ability to produce 3-HP by the Pdu pathway (employing the PduP, PduL, and PduW enzymes). Here, we report the production of 3-HP in E. coli by using the Pdu pathway from K. pneumoniae as a synthetic pathway. Moreover, a strain harboring a dual synthetic pathways (ALDH and Pdu) exhibited a 70% increase in 3-HP titer compared to one harboring the ALDH pathway alone (56.1 ± 0.736 mM and 33.1 ± 0.920 mM, respectively). To our knowledge, this is the first report of 3-HP production by E. coli harboring the Pdu pathway, with the dual synthetic pathway showing the highest yield ever reported by batch culture [54.1% (mol/mol)].