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Production of 1-octanol in Escherichia coli by a high flux thioesterase route
Open accessAbstract
1-octanol is a valuable molecule in the chemical industry, where it is used as a plasticizer, as a precursor in the production of linear low-density polyethylene (LLDPE), and as a growth inhibitor of tobacco plant suckers. Due to the low availability of eight-carbon acyl chains in natural lipid feedstocks and the selectivity challenges in petrochemical routes to medium-chain fatty alcohols,1-octanol sells for the highest price among the fatty alcohol products. As an alternative, metabolic engineers have pursued sustainable 1-octanol production via engineered microbes. Here, we report demonstration of gram per liter titers in the model bacterium Escherichia coli via the development of a pathway composed of a thioesterase, an acyl-CoA synthetase, and an acyl-CoA reductase. In addition, the impact of deleting fermentative pathways was explored E. coli K12 MG1655 strain for production of octanoic acid, a key octanol precursor. In order to overcome metabolic flux barriers, bioprospecting experiments were performed to identify acyl-CoA synthetases with high activity towards octanoic acid and acyl-CoA reductases with high activity to produce 1-octanol from octanoyl-CoA. Titration of expression of key pathway enzymes was performed and a strain with the full pathway integrated on the chromosome was created. The final strain produced 1-octanol at 1.3 g/L titer and a >90% C 8 specificity from glycerol. In addition to the metabolic engineering efforts, this work addressed some of the technical challenges that arise when quantifying 1-octanol produced from cultures grown under fully aerobic conditions where evaporation and stripping are prevalent.
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Engineered E. coli strains have achieved 1-octanol titres up to 1.3 g/L with greater than 90% C8 selectivity from glycerol in batch fermentations of 24-48 h.
“For context, engineered E. coli strains have achieved 1-octanol titres of up to 1.3 g/L with greater than 90% C8 selectivity from glycerol in batch fermentations of 24–48 h [179], representing an approximately 2.5-fold higher titre than the cyanobacterial result but achieved from an organic carbon feedstock in a fraction of the cultivation time.”
From Cyanobacteria as a Photosynthetic Chassis for Metabolic Pathway Engineering with Heterologous Gene Expression (2026) · cites this paper as [179]
The Abstract reports 1.3 g/L 1-octanol with >90% C8 specificity from glycerol. Results and Discussion (Assembly of the full pathway) says the 1.3 g/L titre was reached after 18 h in shake flasks; Materials and Methods (Fatty alcohol experiments) describes cultivation for up to 24 h after induction. The copy does not support the stated 24–48 h fermentation duration. Page numbers are unavailable in our copy. (LLM, conf=0.87)
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Metadata
- Authors
- Hernández Lozada, N. J., Simmons, T. R., Xu, K., Jindra, M. A., & Pfleger, B. F.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Pfleger, Brian F.
- Venue
- Metabolic Engineering
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 61
- Pages
- 352-359
- ISSN
- 1096-7176 (ISSN-L)
- PMC
- PMC7501170
- OpenAlex
- W3044888145
- Cited by
- 48
- References
- 46
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 10 · 2023: 16 · 2022: 3 · 2021: 3 · 2020: 2
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Metabolic Engineering (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Dow Chemical Company
- National Science Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Biochemical and biochemical processes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- Escherichia coli, thioesterase, acyl-CoA synthetase, octanoic acid, bioprospecting, glycerol, aerobic culture
- MeSH terms
- Thiolester Hydrolases, 1-Octanol, Escherichia coli K12
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