Metabolic engineering: enabling technology for biofuels production.

The biofuels industry is rapidly growing with the goal of providing a sustainable fuel alternative to petroleum products. However, two challenges persist in limiting current biofuels technologies as a viable alternative: (1) the cost of feedstock and (2) the quality of the fuel. Metabolic engineering shows the potential to overcome these two challenges, enabling the bioconversion of cheaper feedstocks into improved fuels in a sustainable and environmentally friendly manner. Metabolic engineering is the systematic attempt to understand, design, and engineer cellular metabolic networks using a wide range of interdisciplinary tools and strategies. It is rapidly emerging as the enabling technology behind the development of the next generation of biofuels. Several examples of current research demonstrate how metabolic engineering has begun to contribute both novel and creative solutions toward bringing promising biofuel technologies to fruition: production of higher chain alcohols, fermentation of lignocellulosic material, and production of fatty acid derivatives. C © 2012 John Wiley & Sons, Ltd.

[1]  G. Stephanopoulos,et al.  Global transcription machinery engineering: a new approach for improving cellular phenotype. , 2007, Metabolic engineering.

[2]  Yong-Su Jin,et al.  Saccharomyces cerevisiae Engineered for Xylose Metabolism Exhibits a Respiratory Response , 2004, Applied and Environmental Microbiology.

[3]  Brian F Pfleger,et al.  A process for microbial hydrocarbon synthesis: Overproduction of fatty acids in Escherichia coli and catalytic conversion to alkanes , 2010, Biotechnology and bioengineering.

[4]  Xuefeng Lu,et al.  Overproduction of free fatty acids in E. coli: implications for biodiesel production. , 2008, Metabolic engineering.

[5]  E. Papoutsakis,et al.  Metabolic engineering of the non-sporulating, non-solventogenic Clostridium acetobutylicum strain M5 to produce butanol without acetone demonstrate the robustness of the acid-formation pathways and the importance of the electron balance. , 2008, Metabolic engineering.

[6]  S. Polasky,et al.  Land Clearing and the Biofuel Carbon Debt , 2008, Science.

[7]  J. Keasling Manufacturing Molecules Through Metabolic Engineering , 2010, Science.

[8]  R. Milo,et al.  Design and analysis of synthetic carbon fixation pathways , 2010, Proceedings of the National Academy of Sciences.

[9]  C. Khosla,et al.  Quantitative analysis and engineering of fatty acid biosynthesis in E. coli. , 2010, Metabolic engineering.

[10]  T. Jeffries,et al.  Deleting the para-nitrophenyl phosphatase (pNPPase), PHO13, in recombinant Saccharomyces cerevisiae improves growth and ethanol production on D-xylose. , 2008, Metabolic engineering.

[11]  M. Adams,et al.  Hydrogenesis in hyperthermophilic microorganisms: implications for biofuels. , 2008, Metabolic engineering.

[12]  G. Stephanopoulos,et al.  Network rigidity and metabolic engineering in metabolite overproduction , 1991, Science.

[13]  N. Sandoval,et al.  Parallel mapping of genotypes to phenotypes contributing to overall biological fitness. , 2008, Metabolic engineering.

[14]  J. Cronan,et al.  Defective Export of a Periplasmic Enzyme Disrupts Regulation of Fatty Acid Synthesis (*) , 1995, The Journal of Biological Chemistry.

[15]  B. Palsson,et al.  The model organism as a system: integrating 'omics' data sets , 2006, Nature Reviews Molecular Cell Biology.

[16]  Jack T Pronk,et al.  High-level functional expression of a fungal xylose isomerase: the key to efficient ethanolic fermentation of xylose by Saccharomyces cerevisiae? , 2003, FEMS yeast research.

[17]  J. Keasling,et al.  Microbial production of fatty-acid-derived fuels and chemicals from plant biomass , 2010, Nature.

[18]  S. Polasky,et al.  Environmental, economic, and energetic costs and benefits of biodiesel and ethanol biofuels. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Kevin V. Solomon,et al.  Engineering microbes with synthetic biology frameworks. , 2008, Trends in biotechnology.

[20]  N. Ho,et al.  Genetically Engineered SaccharomycesYeast Capable of Effective Cofermentation of Glucose and Xylose , 1998, Applied and Environmental Microbiology.

[21]  G. Stephanopoulos Metabolic fluxes and metabolic engineering. , 1999, Metabolic engineering.

[22]  D. Pimentel,et al.  Ethanol Production Using Corn, Switchgrass, and Wood; Biodiesel Production Using Soybean and Sunflower , 2005 .

[23]  M. Inui,et al.  Expression of Clostridium acetobutylicum butanol synthetic genes in Escherichia coli , 2008, Applied Microbiology and Biotechnology.

[24]  Andreas S Bommarius,et al.  Cellulase kinetics as a function of cellulose pretreatment. , 2008, Metabolic engineering.

[25]  L. Lynd,et al.  Likely features and costs of mature biomass ethanol technology , 1996 .

[26]  T. Jeffries,et al.  Engineering yeasts for xylose metabolism. , 2006, Current opinion in biotechnology.

[27]  G. Stephanopoulos,et al.  Engineering Yeast Transcription Machinery for Improved Ethanol Tolerance and Production , 2006, Science.

[28]  F. Srienc,et al.  Elementary mode analysis: a useful metabolic pathway analysis tool for characterizing cellular metabolism , 2009, Applied Microbiology and Biotechnology.

[29]  J. Förster,et al.  In silico aided metabolic engineering of Saccharomyces cerevisiae for improved bioethanol production. , 2006, Metabolic engineering.

[30]  Havva Balat,et al.  A critical review of bio-diesel as a vehicular fuel. , 2008 .

[31]  G. Stephanopoulos Challenges in Engineering Microbes for Biofuels Production , 2007, Science.

[32]  J. Liao,et al.  Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels , 2008, Nature.

[33]  Albert J. Vilella,et al.  Cellodextrin Transport in Yeast for Improved Biofuel Production , 2010, Science.

[34]  Keith E. J. Tyo,et al.  Expanding the metabolic engineering toolbox: more options to engineer cells. , 2007, Trends in biotechnology.

[35]  J. Bailey,et al.  Toward a science of metabolic engineering , 1991, Science.

[36]  G. Stephanopoulos,et al.  Selection and optimization of microbial hosts for biofuels production. , 2008, Metabolic engineering.

[37]  A J Sinskey,et al.  Metabolic engineering--methodologies and future prospects. , 1993, Trends in biotechnology.

[38]  Rainer Kalscheuer,et al.  Microdiesel: Escherichia coli engineered for fuel production. , 2006, Microbiology.

[39]  Kevin M. Smith,et al.  Metabolic engineering of Escherichia coli for 1-butanol production. , 2008, Metabolic engineering.

[40]  L. Ingram,et al.  Genetic engineering of ethanol production in Escherichia coli , 1987, Applied and environmental microbiology.

[41]  Yong-Su Jin,et al.  Engineered Saccharomyces cerevisiae capable of simultaneous cellobiose and xylose fermentation , 2010, Proceedings of the National Academy of Sciences.

[42]  J. Liao,et al.  Metabolic engineering of Escherichia coli for 1-butanol and 1-propanol production via the keto-acid pathways. , 2008, Metabolic engineering.

[43]  William J. Bosl,et al.  Systems biology by the rules: hybrid intelligent systems for pathway modeling and discovery , 2007, BMC Systems Biology.

[44]  S. Sawayama,et al.  Ethanol production from xylose in engineered Saccharomyces cerevisiae strains: current state and perspectives , 2009, Applied Microbiology and Biotechnology.

[45]  Ka-Yiu San,et al.  Replacing Escherichia coli NAD-dependent glyceraldehyde 3-phosphate dehydrogenase (GAPDH) with a NADP-dependent enzyme from Clostridium acetobutylicum facilitates NADPH dependent pathways. , 2008, Metabolic engineering.

[46]  R. Gonzalez,et al.  Engineering Escherichia coli for the efficient conversion of glycerol to ethanol and co-products. , 2008, Metabolic engineering.

[47]  Bryce J. Stokes,et al.  Biomass as Feedstock for A Bioenergy and Bioproducts Industry: The Technical Feasibility of a Billion-Ton Annual Supply , 2005 .