Abstract
Escherichia coli is currently used by many research institutions and companies around the world as a platform organism for the development of bio-based production processes for bulk biochemicals. A given bulk biochemical bioprocess must be economically competitive with current production routes. Ideally the viability of each bioprocess should be evaluated prior to commencing research, both by metabolic network analysis (to determine the maximum theoretical yield of a given biocatalyst) and by techno-economic analysis (TEA; to determine the conditions required to make the bioprocess cost-competitive). However, these steps are rarely performed. Here we examine theoretical yields and review available TEA for bulk biochemical production in E. coli. In addition, we examine fermentation feedstocks and review recent strain engineering approaches to achieve industrially-relevant production, using examples for which TEA has been performed: ethanol, poly-3-hydroxybutyrate, and 1,3-propanediol.
Similar content being viewed by others
References
Aldor IS, Keasling JD (2003) Process design for microbial plastic factories: metabolic engineering of polyhydroxyalkanoates. Curr Opin Biotechnol 14:475–483
Alper H, Stephanopoulos G (2007) Global transcription machinery engineering: a new approach for improving cellular phenotype. Metab Eng 9:258–267
Archer C, Kim J, Jeong H, Park J, Vickers C, Lee S,Nielsen L (2011) The genome sequence of E. coli W ATCC 9637: comparative genome analysis and an improved genome-scale model of E. coli. BMC Genomics 12:9. doi:10.1186/1471-2164-1112-1189
Arifin Y, Sabri S, Sugiarto H, Krömer JO, Vickers CE,Nielsen LK (2011) Deletion of cscR in Escherichia coli W improves growth and poly-3-hydroxyburyrate (PHB) production from sucrose in fed batch culture. J Biotechnol. doi:10.1016/j.jbiotec.2011.07.003
Atsumi S, Cann AF, Connor MR, Shen CR, Smith KM, Brynildsen MP, Chou KJY, Hanai T, Liao JC (2008) Metabolic engineering of Escherichia coli for 1-butanol production. Metab Eng 10:305–311
Banner T, Fosmer A, Jessen H, Marasco E, Rush B, Veldhouse J, de Souza M (2011) Microbial bioprocesses for industrial-scale chemical production. In: Tao J, Kazlauskas R (eds) Biocatalysis for green chemistry and chemical process development. Wiley, Hoboken, pp 429–467
Blanch HW, Simmons BA, Klein-Marcuschamer D (2011) Biomass deconstruction to sugars. Biotechnol J 6:1086–1102
Bruschi M, Boyes S, Sugiarto H, Nielsen LK,Vickers CE (2011) A universal transferrable sucrose utilization approach for non-sucrose-utilizing E. coli strains. Biotech Adv. doi:10.1016/j.biotechadv.2011.1008.1019
Chen G-Q (2009) A microbial polyhydroxyalkanoates (PHA) based bio- and materials industry. Chem Soc Rev 38:2434–2446
Chen K, Iverson A, Garza E, Grayburn W, Zhou S (2009) Metabolic evolution of non-transgenic Escherichia coli SZ420 for enhanced homoethanol fermentation from xylose. Biotechnol Lett 32:87–96
Chinen A, Kozlov YI, Hara Y, Izui H, Yasueda H (2007) Innovative metabolic pathway design for efficient l-glutamate production by suppressing CO2 emission. J Biosci Bioeng 103:262–269
Choi JI, Lee SY (1997) Process analysis and economic evaluation for poly(3-hydroxybutyrate) production by fermentation. Bioprocess Eng 17:335–342
Choi JI, Lee SY (1999) High-level production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) by fed-batch culture of recombinant Escherichia coli. Appl Environ Microbiol 65:4363–4368
Dhamankar H, Prather KLJ (2011) Microbial chemical factories: recent advances in pathway engineering for synthesis of value added chemicals. Curr Opin Struc Biol 21:488–494
Dien BS, Cotta MA, Jeffries TW (2003) Bacteria engineered for fuel ethanol production: current status. Appl Microbiol Biotechnol 63:258–266
Dueber JE, Wu GC, Malmirchegini GR, Moon TS, Petzold CJ, Ullal AV, Prather KLJ, Keasling JD (2009) Synthetic protein scaffolds provide modular control over metabolic flux. Nat Biotech 27:753–759
Edwards MC, Henriksen ED, Yomano LP, Gardner BC, Sharma LN, Ingram LO, Doran Peterson J (2011) Addition of genes for cellobiase and pectinolytic activity in Escherichia coli for fuel ethanol production from pectin-rich lignocellulosic biomass. Appl Environ Microbiol 77:5184–5191
Erickson B, Nelson JE,Winters P (2011) Perspective on opportunities in industrial biotechnology in renewable chemicals. Biotechnol J. doi:10.1002/biot.201100069
Feist AM, Palsson BO (2008) The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli. Nat Biotechnol 26:659–667
Fu Y-Q, Li S, Chen Y, Xu Q, Huang H, Sheng X-Y (2010) Enhancement of fumaric acid production by Rhizopus oryzae using a two-stage dissolved oxygen control strategy. Appl Biochem Biotechnol 162:1031–1038
Gonzalez R, Campbell P, Wong M (2010) Production of ethanol from thin stillage by metabolically engineered Escherichia coli. Biotechnol Lett 32:405–411
Huerta-Beristain G, Utrilla J, Hernandez-Chavez G, Bolivar F, Gosset G, Martinez A (2008) Specific ethanol production rate in ethanologenic Escherichia coli strain KO11 is limited by pyruvate decarboxylase. J Mol Microbiol Biotechnol 15:55–64
IEA (2004) Biofuels for transport: an international perspective. International Energy Agency, Paris
Kanehisa M, Goto S (2000) KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28:27–30
Kang Z, Wang Q, Zhang H, Qi Q (2008) Construction of a stress-induced system in Escherichia coli for efficient polyhydroxyalkanoates production. Appl Microbiol Biotechnol 79:203–208
Kang Z, Gao C, Wang Q, Liu H, Qi Q (2010) A novel strategy for succinate and polyhydroxybutyrate co-production in Escherichia coli. Bioresour Technol 101:7675–7678
Keasling JD (2008) Synthetic biology for synthetic chemistry. ACS Chem Biol 3:64–76
Khanna S, Srivastava AK (2005) Recent advances in microbial polyhydroxyalkanoates. Process Biochem 40:607–619
Kind S, Kreye S, Wittmann C (2011) Metabolic engineering of cellular transport for overproduction of the platform chemical 1,5-diaminopentane in Corynebacterium glutamicum. Metab Eng 13:617–627
Klein-Marcuschamer D, Oleskowicz-Popiel P, Simmons BA, Blanch HW (2010) Technoeconomic analysis of biofuels: a wiki-based platform for lignocellulosic biorefineries. Biomass Bioenerg 34:1914–1921
Klein-Marcuschamer D, Holmes B, Simmons BA, Blanch HW (2011) Biofuel economics in plant biomass conversion. Wiley, New York, pp 329–354
Krömer JO, Wittmann C, Schröder H, Heinzle E (2006) Metabolic pathway analysis for rational design of l-methionine production by Escherichia coli and Corynebacterium glutamicum. Metab Eng 8:353–369
Kummel A, Panke S, Heinemann M (2006) Systematic assignment of thermodynamic constraints in metabolic network models. BMC Bioinform 7:512. doi:510.1186/1471-2105-1187-1512
Kurian JV (2005) A new polymer platform for the future—Sorona(R) from corn derived 1,3-propanediol. J Polym Environ 13:159–167
Lee SY (1996) Bacterial polyhydroxyalkanoates. Biotechnol Bioeng 49:1–14
Lee SY, Chang HN (1993) High cell density cultivation of Escherichia coli W using sucrose as a carbon source. Biotechnol Lett 15:971–974
Lee SH, Park S, Lee S, Hong S (2008) Biosynthesis of enantiopure (S)-3-hydroxybutyric acid in metabolically engineered Escherichia coli. Appl Microbiol Biotechnol 79:633–641
Li R, Chen Q, Wang P, Qi Q (2007a) A novel-designed Escherichia coli for the production of various polyhydroxyalkanoates from inexpensive substrate mixture. Appl Microbiol Biotechnol 75:1103–1109
Li R, Zhang H, Qi Q (2007b) The production of polyhydroxyalkanoates in recombinant Escherichia coli. Bioresour Technol 98:2313–2320
Liu Q, Ouyang SP, Chung A, Wu Q, Chen GQ (2007) Microbial production of R-3-hydroxybutyric acid by recombinant E.coli harboring genes of phbA, phbB, and tesB. Appl Microbiol Biotechnol 76:811–818
Moon TS, Yoon SH, Lanza AM, Roy-Mayhew JD, Prather KL (2009) Production of glucaric acid from a synthetic pathway in recombinant Escherichia coli. Appl Environ Microbiol 75:589–595
Moon TS, Dueber JE, Shiue E, Prather KLJ (2010) Use of modular, synthetic scaffolds for improved production of glucaric acid in engineered E. coli. Metab Eng 12:298–305
Naik S, Gopal SKV, Somal P (2008) Bioproduction of polyhydroxyalkanoates from bacteria: a metabolic approach. World J Microb Biot 24:2307–2314
Nakamura CE, Whited GM (2003) Metabolic engineering for the microbial production of 1,3-propanediol. Curr Opin Biotechnol 14:454–459
Ohta K, Beall DS, Mejia JP, Shanmugam KT, Ingram LO (1991) Genetic improvement of Escherichia coli for ethanol production: chromosomal integration of Zymomonas mobilis genes encoding pyruvate decarboxylase and alcohol dehydrogenase II. Appl Environ Microbiol 57:893–900
Park JH, Lee SY (2010) Metabolic pathways and fermentative production of l-aspartate family amino acids. Biotechnol J 5:560–577
Park S-D, Lee J-Y, Sim S-Y, Kim Y, Lee H-S (2007) Characteristics of methionine production by an engineered Corynebacterium glutamicum strain. Metab Eng 9:327–336
Park JH, Lee SY, Kim TY, Kim HU (2008) Application of systems biology for bioprocess development. Trends Biotechnol 26:404–412
Patel M, Crank M, Dornburg V, Hermann B, Roes L, Hüsing B, Overbeek L, Terragni F,Recchia E (2006) Medium and long-term opportunities and risks of the biotechnological production of bulk chemicals from renewable resources—the potential of white biotechnology. European Commission
Penloglou G, Chatzidoukas C, Kiparissides C (2011) Microbial production of polyhydroxybutyrate with tailor-made properties: an integrated modelling approach and experimental validation. Biotech Adv. doi:10.1016/j.biotechadv.2011.1006.1021
Peters D (2006) Carbohydrates for fermentation. Biotechnol J 1:806–814
Prather KL, Martin CH (2008) De novo biosynthetic pathways: rational design of microbial chemical factories. Curr Opin Biotechnol 19:468–474
Renouf MA, Wegener MK, Nielsen LK (2008) An environmental life cycle assessment comparing Australian sugarcane with US corn and UK sugar beet as producers of sugars for fermentation. Biomass Bioenergy 32:1144–1155
Rude MA, Schirmer A (2009) New microbial fuels: a biotech perspective. Curr Opin Microbiol 12:274–281
Shukla VB, Zhou S, Yomano LP, Shanmugam KT, Preston JF, Ingram LO (2004) Production of d-lactate from sucrose and molasses. Biotechnol Lett 26:689–693
Solaiman D, Ashby R, Foglia T, Marmer W (2006) Conversion of agricultural feedstock and coproducts into poly(hydroxyalkanoates). Appl Microbiol Biotechnol 71:783–789
Steinbüchel A, Lütke-Eversloh T (2003) Metabolic engineering and pathway construction for biotechnological production of relevant polyhydroxyalkanoates in microorganisms. Biochem Eng J 16:81–96
Steinbüchel A, Aerts K, Babel W, Follner C, Liebergesell M, Madkour MH, Mayer F, Pieper-Furst U, Pries A, Valentin HE et al (1995) Considerations on the structure and biochemistry of bacterial polyhydroxyalkanoic acid inclusions. Can J Microbiol 41(1):94–105
Stephanopoulos G, Alper H, Moxley J (2004) Exploiting biological complexity for strain improvement through systems biology. Nat Biotechnol 22:1261–1267
Tao L, Aden A (2009) The economics of current and future biofuels. In Vitro Cell Dev Biol 45:199–217
Van Wegen RJ, Ling Y, Middelberg APJ (1998) Industrial production of polyhydroxyalkanoates using Escherichia coli: an economic analysis. Chem Eng Res Des 76:417–426
Verlinden RAJ, Hill DJ, Kenward MA, Williams CD, Radecka I (2007) Bacterial synthesis of biodegradable polyhydroxyalkanoates. J Appl Microbiol 102:1437–1449
Vickers CE, Blank LM, Kromer JO (2010) Chassis cells for industrial biochemical production. Nat Chem Biol 6:875–877
von Kamp A, Schuster S (2006) Metatool 5.0: fast and flexible elementary modes analysis. Bioinformatics 22:1930–1931
von Sivers M, Zacchi G, Olsson L, Hahn-Hügerdal B (1994) Cost analysis of ethanol production from willow using recombinant Escherichia coli. Biotechnol Progr 10:555–560
Wang F, Lee S (1997) Production of poly(3-hydroxybutyrate) by fed-batch culture of filamentation-suppressed recombinant Escherichia col. Appl Environ Microbiol 63:4765–4769
Wang ZX, Zhuge J, Fang H, Prior BA (2001) Glycerol production by microbial fermentation: a review. Biotechnol Adv 19:201–223
Wang C, Yoon S-H, Jang H-J, Chung Y-R, Kim J-Y, Choi E-S, Kim S-W (2011a) Metabolic engineering of Escherichia coli for α-farnesene production. Metab Eng 13:648–655
Wang J, Zhu J, Bennett GN, San KY (2011b) Succinate production from sucrose by metabolic engineered Escherichia coli strains under aerobic conditions. Biotechnol Prog 27:1242–1247
Wang X, Miller EN, Yomano LP, Zhang X, Shanmugam KT, Ingram LO (2011c) Overexpression of NADH-dependent oxidoreductase fucO increases furfural tolerance in Escherichia coli strains engineered for the production of ethanol and lactate. Appl Environ Microbiol 77:5132–5140
Whited GM, Feher FJ, Benko DA, Cervin MA, Chotani GK, McAuliffe JC, LaDuca RJ, Ben-Shoshan EA, Sanford KJ (2010) TECHNOLOGY UPDATE: development of a gas-phase bioprocess for isoprene-monomer production using metabolic pathway engineering. Ind Biotechnol 6:152–163
Willke T, Vorlop K (2008) Biotransformation of glycerol into 1,3-propanediol. Eur J Lipid Sci Tech 110:831–840
Winkler J, Rehmann M, Kao K (2010) Novel Escherichia coli hybrids with enhanced butanol tolerance. Biotechnol Lett 32:915–920
Yahiro K, Takahama T, Park YS, Okabe M (1995) Breeding of Aspergillus terreus mutant TN-484 for itaconic acid production with high yield. J Ferment Bioeng 79:506–508
Yazdani SS, Gonzalez R (2008) Engineering Escherichia coli for the efficient conversion of glycerol to ethanol and co-products. Metab Eng 10:340–351
Yim H, Haselbeck R, Niu W, Pujol-Baxley C, Burgard A, Boldt J, Khandurina J, Trawick JD, Osterhout RE, Stephen R, Estadilla J, Teisan S, Schreyer HB, Andrae S, Yang TH, Lee SY, Burk MJ, Van Dien S (2011) Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol. Nat Chem Biol 7:445–452
Yomano L, York S, Zhou S, Shanmugam K, Ingram L (2008) Re-engineering Escherichia coli for ethanol production. Biotechnol Lett 30:2097–2103
Zhang X, Jantama K, Moore J, Shanmugam K, Ingram L (2007) Production of l-alanine by metabolically engineered Escherichia coli. Appl Microbiol Biotechnol 77:355–366
Zhang X, Wang X, Shanmugam KT, Ingram LO (2011) l-malate production by metabolically engineered Escherichia coli. Appl Environ Microbiol 77:427–434
Zhou S, Iverson A, Grayburn W (2008) Engineering a native homoethanol pathway in Escherichia coli B for ethanol production. Biotechnol Lett 30:335–342
Acknowledgments
CEV was supported by a Queensland State Government Smart Futures Fellowship and the Queensland State Government National and International Research Alliance Program. The work of DKM was partly funded by the DOE Joint BioEnergy Institute (http://www.jbei.org) supported by the U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research, through contract DE-AC02-05CH11231 between Lawrence Berkeley National Laboratory and the U.S. Department of Energy.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
10529_2011_821_MOESM1_ESM.pdf
Metabolic network of Escherichia coli modified from Krömer et al. (2006) by addition of respective product pathways identified in KEGG (Kanehisa and Goto 2000). Central carbon metabolism and biomass formation are given. The network is ready to be extended by new production pathways. The syntax is compatible with Metatool 5.1 (http://pinguin.biologie.uni-jena.de/bioinformatik/networks/). (PDF 52 kb)
Rights and permissions
About this article
Cite this article
Vickers, C.E., Klein-Marcuschamer, D. & Krömer, J.O. Examining the feasibility of bulk commodity production in Escherichia coli . Biotechnol Lett 34, 585–596 (2012). https://doi.org/10.1007/s10529-011-0821-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10529-011-0821-3