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Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels
Abstract
Global energy and environmental problems have stimulated increased efforts towards synthesizing biofuels from renewable resources. Compared to the traditional biofuel, ethanol, higher alcohols offer advantages as gasoline substitutes because of their higher energy density and lower hygroscopicity. In addition, branched-chain alcohols have higher octane numbers compared with their straight-chain counterparts. However, these alcohols cannot be synthesized economically using native organisms. Here we present a metabolic engineering approach using Escherichia coli to produce higher alcohols including isobutanol, 1-butanol, 2-methyl-1-butanol, 3-methyl-1-butanol and 2-phenylethanol from glucose, a renewable carbon source. This strategy uses the host's highly active amino acid biosynthetic pathway and diverts its 2-keto acid intermediates for alcohol synthesis. In particular, we have achieved high-yield, high-specificity production of isobutanol from glucose. The strategy enables the exploration of biofuels beyond those naturally accumulated to high quantities in microbial fermentation.
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“The cyanobacterial cumulative titre of 1247 mg/L over 58 days equates to approximately 21.5 mg L−1 d−1 average daily productivity, compared to approximately 10,900 mg L−1 d−1 for E. coli—a several-hundred-fold difference reflecting light-dependent growth constraints rather than poor pathway design.”
From Cyanobacteria as a Photosynthetic Chassis for Metabolic Pathway Engineering with Heterologous Gene Expression (2026) · cites this paper as [175]
In the citing paper
“The longer chain alcohols possess higher energy content and can be stored and transported easier than ethanol (Atsumi et al. 2008).”
From Renewable energy from Cyanobacteria: energy production optimization by metabolic pathway engineering (2011) · cites this paper as Atsumi et al. 2008
In the citing paper
“The production of longer chain alcohols (C5–C–8) in E. coli bacteria has been achieved by the overproduction of 2-keto acids, intermediates of the amino acid biosynthesis. These intermediates were later converted to butanol derivatives by the heterologous expression of 2-keto acid decarboxylase and alcohol dehydrogenase (Atsumi et al. 2008; Zhang et al. 2008).”
From Renewable energy from Cyanobacteria: energy production optimization by metabolic pathway engineering (2011) · cites this paper as Atsumi et al. 2008
In the citing paper
“It is difficult to identify a microorganism suitable to produce C5 and other C4 substituted alcohols from sugar glucose while minimising the steps in the process and making it cost effective [141].”
From Investigation of Biofuel as a Potential Renewable Energy Source (2021) · cites this paper as [141]
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Self-citation
Metadata
- Authors
- Atsumi, S., Hanai, T., & Liao, J. C.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Liao, James C.
- Venue
- Nature
- Published
- 2008-01
- Volume
- 451
- Issue
- 7174
- Pages
- 86-89
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1978119727
- Cited by
- 1,945
- References
- 32
- Citations by year
- 2026: 50 · 2025: 55 · 2024: 66 · 2023: 72 · 2022: 113 · 2021: 111 · 2020: 121 · 2019: 86 · 2018: 98 · 2017: 103 · 2016: 131 · 2015: 137 · 2014: 148 · 2013: 153 · 2012: 162
- FWCI
- 46.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- U.S. Department of Energy
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Physical Sciences › Engineering › Biomedical Engineering › Biofuel production and bioconversion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Biochemical and biochemical processes
- Keywords
- isobutanol, n-butanol, 2-phenylethanol, Escherichia coli metabolic engineering, glucose fermentation, biofuels, gasoline substitute, octane number
- MeSH terms
- Butanols, Bioelectric Energy Sources, Escherichia coli, Fermentation, Genetic Engineering, Glucose
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