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Author

Shota Atsumi

Bio: Shota Atsumi is an academic researcher from University of California, Davis. The author has contributed to research in topics: Isobutanol & Escherichia coli. The author has an hindex of 37, co-authored 76 publications receiving 8041 citations. Previous affiliations of Shota Atsumi include University of California & University of California, Los Angeles.


Papers
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Journal ArticleDOI
03 Jan 2008-Nature
TL;DR: This strategy uses the host’s highly active amino acid biosynthetic pathway and diverts its 2-keto acid intermediates for alcohol synthesis to achieve high-yield, high-specificity production of isobutanol from glucose.
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.

1,955 citations

Journal ArticleDOI
TL;DR: A synthetic pathway is engineered in Escherichia coli and the production of 1-butanol is demonstrated from this non-native user-friendly host, showing promise for using E. coli for 1- butanol production.

900 citations

Journal ArticleDOI
TL;DR: The genetically engineered Synechococcus elongatus PCC7942 strain is genetically engineered to produce isobutyraldehyde and isobutanol directly from CO2 and increased productivity by overexpression of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco).
Abstract: Global climate change has stimulated efforts to reduce CO(2) emissions. One approach to addressing this problem is to recycle CO(2) directly into fuels or chemicals using photosynthesis. Here we genetically engineered Synechococcus elongatus PCC7942 to produce isobutyraldehyde and isobutanol directly from CO(2) and increased productivity by overexpression of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco). Isobutyraldehyde is a precursor for the synthesis of other chemicals, and isobutanol can be used as a gasoline substitute. The high vapor pressure of isobutyraldehyde allows in situ product recovery and reduces product toxicity. The engineered strain remained active for 8 d and produced isobutyraldehyde at a higher rate than those reported for ethanol, hydrogen or lipid production by cyanobacteria or algae. These results underscore the promise of direct bioconversion of CO(2) into fuels and chemicals, which bypasses the need for deconstruction of biomass.

822 citations

Journal ArticleDOI
TL;DR: To the authors' knowledge, this work is the first to produce isopropanol in E. coli, and the titer exceeded that from the native producers.
Abstract: A synthetic pathway was engineered in Escherichia coli to produce isopropanol by expressing various combinations of genes from Clostridium acetobutylicum ATCC 824, E. coli K-12 MG1655, Clostridium beijerinckii NRRL B593, and Thermoanaerobacter brockii HTD4. The strain with the combination of C. acetobutylicum thl (acetyl-coenzyme A [CoA] acetyltransferase), E. coli atoAD (acetoacetyl-CoA transferase), C. acetobutylicum adc (acetoacetate decarboxylase), and C. beijerinckii adh (secondary alcohol dehydrogenase) achieved the highest titer. This strain produced 81.6 mM isopropanol in shake flasks with a yield of 43.5% (mol/mol) in the production phase. To our knowledge, this work is the first to produce isopropanol in E. coli, and the titer exceeded that from the native producers.

375 citations

Journal ArticleDOI
TL;DR: This work systematically developed the 2,3-butanediol (23BD) biosynthetic pathway in Synechococcus elongatus PCC7942 as a model system to establish design methods for efficient exogenous chemical production in cyanobacteria, and identified 23BD as a target chemical with low host toxicity.
Abstract: Conversion of CO2 for the synthesis of chemicals by photosynthetic organisms is an attractive target for establishing independence from fossil reserves. However, synthetic pathway construction in cyanobacteria is still in its infancy compared with model fermentative organisms. Here we systematically developed the 2,3-butanediol (23BD) biosynthetic pathway in Synechococcus elongatus PCC7942 as a model system to establish design methods for efficient exogenous chemical production in cyanobacteria. We identified 23BD as a target chemical with low host toxicity, and designed an oxygen-insensitive, cofactor-matched biosynthetic pathway coupled with irreversible enzymatic steps to create a driving force toward the target. Production of 23BD from CO2 reached 2.38 g/L, which is a significant increase for chemical production from exogenous pathways in cyanobacteria. This work demonstrates that developing strong design methods can continue to increase chemical production in cyanobacteria.

345 citations


Cited by
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Journal ArticleDOI
10 May 2012-Nature
TL;DR: Applications of protein-engineered biocatalysts ranging from commodity chemicals to advanced pharmaceutical intermediates that use enzyme catalysis as a key step are discussed.
Abstract: Over the past ten years, scientific and technological advances have established biocatalysis as a practical and environmentally friendly alternative to traditional metallo- and organocatalysis in chemical synthesis, both in the laboratory and on an industrial scale. Key advances in DNA sequencing and gene synthesis are at the base of tremendous progress in tailoring biocatalysts by protein engineering and design, and the ability to reorganize enzymes into new biosynthetic pathways. To highlight these achievements, here we discuss applications of protein-engineered biocatalysts ranging from commodity chemicals to advanced pharmaceutical intermediates that use enzyme catalysis as a key step.

1,985 citations

Journal ArticleDOI
TL;DR: A predictive method for designing synthetic ribosome binding sites is developed, enabling a rational control over the protein expression level, and is demonstrated by rationally optimizing protein expression to connect a genetic sensor to a synthetic circuit.
Abstract: Microbial engineering often requires fine control over protein expression--for example, to connect genetic circuits or control flux through a metabolic pathway. To circumvent the need for trial and error optimization, we developed a predictive method for designing synthetic ribosome binding sites, enabling a rational control over the protein expression level. Experimental validation of >100 predictions in Escherichia coli showed that the method is accurate to within a factor of 2.3 over a range of 100,000-fold. The design method also correctly predicted that reusing identical ribosome binding site sequences in different genetic contexts can result in different protein expression levels. We demonstrate the method's utility by rationally optimizing protein expression to connect a genetic sensor to a synthetic circuit. The proposed forward engineering approach should accelerate the construction and systematic optimization of large genetic systems.

1,611 citations

Journal ArticleDOI
28 Jan 2010-Nature
TL;DR: The engineering of Escherichia coli is demonstrated to produce structurally tailored fatty esters (biodiesel), fatty alcohols, and waxes directly from simple sugars, a step towards producing these compounds directly from hemicellulose, a major component of plant-derived biomass.
Abstract: Increasing energy costs and environmental concerns have emphasized the need to produce sustainable renewable fuels and chemicals. Major efforts to this end are focused on the microbial production of high-energy fuels by cost-effective 'consolidated bioprocesses'. Fatty acids are composed of long alkyl chains and represent nature's 'petroleum', being a primary metabolite used by cells for both chemical and energy storage functions. These energy-rich molecules are today isolated from plant and animal oils for a diverse set of products ranging from fuels to oleochemicals. A more scalable, controllable and economic route to this important class of chemicals would be through the microbial conversion of renewable feedstocks, such as biomass-derived carbohydrates. Here we demonstrate the engineering of Escherichia coli to produce structurally tailored fatty esters (biodiesel), fatty alcohols, and waxes directly from simple sugars. Furthermore, we show engineering of the biodiesel-producing cells to express hemicellulases, a step towards producing these compounds directly from hemicellulose, a major component of plant-derived biomass.

1,344 citations

Journal ArticleDOI
TL;DR: The de novo engineering of genetic circuits, biological modules and synthetic pathways is beginning to address these crucial problems and is being used in related practical applications.
Abstract: Synthetic biology is bringing together engineers and biologists to design and build novel biomolecular components, networks and pathways, and to use these constructs to rewire and reprogram organisms. These re-engineered organisms will change our lives over the coming years, leading to cheaper drugs, 'green' means to fuel our cars and targeted therapies for attacking 'superbugs' and diseases, such as cancer. The de novo engineering of genetic circuits, biological modules and synthetic pathways is beginning to address these crucial problems and is being used in related practical applications.

1,247 citations

Journal ArticleDOI
TL;DR: The present review describes the advantages of microalgae for the production of biofuels and various bioactive compounds and discusses culturing parameters.
Abstract: Microalgae have recently attracted considerable interest worldwide, due to their extensive application potential in the renewable energy, biopharmaceutical, and nutraceutical industries. Microalgae are renewable, sustainable, and economical sources of biofuels, bioactive medicinal products, and food ingredients. Several microalgae species have been investigated for their potential as value-added products with remarkable pharmacological and biological qualities. As biofuels, they are a perfect substitute to liquid fossil fuels with respect to cost, renewability, and environmental concerns. Microalgae have a significant ability to convert atmospheric CO2 to useful products such as carbohydrates, lipids, and other bioactive metabolites. Although microalgae are feasible sources for bioenergy and biopharmaceuticals in general, some limitations and challenges remain, which must be overcome to upgrade the technology from pilot-phase to industrial level. The most challenging and crucial issues are enhancing microalgae growth rate and product synthesis, dewatering algae culture for biomass production, pretreating biomass, and optimizing the fermentation process in case of algal bioethanol production. The present review describes the advantages of microalgae for the production of biofuels and various bioactive compounds and discusses culturing parameters.

1,125 citations