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Systems metabolic engineering of Escherichia coli for hyper-production of 5‑aminolevulinic acid
- Source :
- Biotechnology for Biofuels and Bioproducts, Vol 16, Iss 1, Pp 1-16 (2023)
- Publication Year :
- 2023
- Publisher :
- BMC, 2023.
-
Abstract
- Abstract Background 5-Aminolevulinic acid (5-ALA) is a promising biostimulant, feed nutrient, and photodynamic drug with wide applications in modern agriculture and therapy. Although microbial production of 5-ALA has been improved realized by using metabolic engineering strategies during the past few years, there is still a gap between the present production level and the requirement of industrialization. Results In this study, pathway, protein, and cellular engineering strategies were systematically employed to construct an industrially competitive 5-ALA producing Escherichia coli. Pathways involved in precursor supply and product degradation were regulated by gene overexpression and synthetic sRNA-based repression to channel metabolic flux to 5-ALA biosynthesis. 5-ALA synthase was rationally engineered to release the inhibition of heme and improve the catalytic activity. 5-ALA transport and antioxidant defense systems were targeted to enhance cellular tolerance to intra- and extra-cellular 5-ALA. The final engineered strain produced 30.7 g/L of 5-ALA in bioreactors with a productivity of 1.02 g/L/h and a yield of 0.532 mol/mol glucose, represent a new record of 5-ALA bioproduction. Conclusions An industrially competitive 5-ALA producing E. coli strain was constructed with the metabolic engineering strategies at multiple layers (protein, pathway, and cellular engineering), and the strategies here can be useful for developing industrial-strength strains for biomanufacturing.
Details
- Language :
- English
- ISSN :
- 27313654
- Volume :
- 16
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Biotechnology for Biofuels and Bioproducts
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.88fa2651067c49288dc02b462e12214f
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s13068-023-02280-9