Abstract
3-Hydroxypropionic acid (3HP), an important three carbon (C3) chemical, is designated as one of the top platform chemicals with an urgent need for improved industrial production. Halomonas bluephagenesis shows the potential as a chassis for competitive bioproduction of various chemicals due to its ability to grow under an open, unsterile and continuous process. Here, we report the strategy for producing 3HP and its copolymer poly(3-hydroxybutyrate-co-3-hydroxypropionate) (P3HB3HP) by the development of H. bluephagenesis. The transcriptome analysis reveals its 3HP degradation and synthesis pathways involving endogenous synthetic enzymes from 1,3-propanediol. Combing the optimized expression of aldehyde dehydrogenase (AldDHb), an engineered H. bluephagenesis strain of whose 3HP degradation pathway is deleted and that overexpresses alcohol dehydrogenases (AdhP) on its genome under a balanced redox state, is constructed with an enhanced 1.3-propanediol-dependent 3HP biosynthetic pathway to produce 154 g L−1 of 3HP with a yield and productivity of 0.93 g g−1 1,3-propanediol and 2.4 g L−1 h−1, respectively. Moreover, the strain could also accumulate 60% poly(3-hydroxybutyrate-co-32–45% 3-hydroxypropionate) in the dry cell mass, demonstrating to be a suitable chassis for hyperproduction of 3HP and P3HB3HP.
Highlights
3-Hydroxypropionic acid (3HP), an important three carbon (C3) chemical, is designated as one of the top platform chemicals with an urgent need for improved industrial production
To enhance the production of 3HP, we need to develop a more suitable producer as the chassis. Another issue occurs during the production of 3HP: under an aerobic condition, glycerol dehydratase (GDHt) is deactivated combined with a downregulated expression of vitamin B1221, while under anaerobic condition, cells were grown poorly, and NAD+, a necessary cofactor of aldehyde dehydrogenase (ALDH), has difficulty to regenerate[21,22,23,24]
The recombinant E. coli S17-1 (p30) produced 1.5 g L−1 and H. bluephagenesis (p30) produced 0.2 g L−1 3HP when grown in conical flasks
Summary
3-Hydroxypropionic acid (3HP), an important three carbon (C3) chemical, is designated as one of the top platform chemicals with an urgent need for improved industrial production. The glycerol to 3HP pathway involves glycerol dehydratase (GDHt) and aldehyde dehydrogenase (ALDH), converting glycerol to 3-hydroxypropionaldehyde and 3HP, respectively[14,15] Traditional microbial chassis such as Escherichia coli or Corynebacterium glutamicum were reported to have the final 3HP concentration of approximately 70 g L−1 16,17. To enhance the production of 3HP, we need to develop a more suitable producer as the chassis Another issue occurs during the production of 3HP: under an aerobic condition, GDHt is deactivated combined with a downregulated expression of vitamin B1221, while under anaerobic condition, cells were grown poorly, and NAD+, a necessary cofactor of ALDH, has difficulty to regenerate[21,22,23,24]. These results paved the way by using 1,3-propanediol as the carbon source to produce 3HP
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