Government Regulation of the Uses of Genetically Modified Algae and Other Microorganisms in Biofuel and Bio-based Chemical Production

  • David J. Glass


Recent years have seen an increased interest in developing genetically modified algae and other microorganisms for use in biofuel and bio-based chemical production. However, this comes at a time when there is uncertainty within the industry and the academic community about how such uses will be regulated by governments in the U.S. and elsewhere in the world, as well as concerns by some observers over the adequacy of existing regulations to cover organisms created using techniques known as synthetic biology. However, a reasonable road map is emerging of a regulatory regime that can allow pilot, demonstration and commercial stage uses of modified microorganisms. In the U.S., regulations of the U.S. Environmental Protection Agency and possibly of the U.S. Department of Agriculture might govern the industrial use of microorganisms in contained photobioreactors or algae in open ponds, and these regulations generally require conducting assessments of the potential environmental risks of such large-scale uses. The EPA regulations include a mechanism by which outdoor experimentation of modified microorganisms can take place in a stepwise approach, with risks assessed as the scale of experimentation increases, which provides an accessible path to exploration of the use of modified algae in open ponds. Such risk assessments will address legitimate questions of potential ecological impact, such as the potential survival and dissemination of the production organism, the potential for heterologous genes to horizontally transfer to indigenous microorganisms, and the chance for other unintended effects on nontarget species. Numerous companies have successfully navigated these regulations, including some recent project approvals in the U.S. and elsewhere in the world.


Genetic modification Genetically modified organism Government regulation Environmental impact Risk assessment Biofuel Bio-based chemical 


  1. Adrio J-L, Demain AL (2010) Recombinant organisms for production of industrial products. Bioengineered 1(2):116–131CrossRefGoogle Scholar
  2. Alexander M (1985) Genetic engineering: ecological consequences. Issues Sci Technol 1(3):57–68Google Scholar
  3. Bergeson LL, Auer CM, Peveler RD (2012) TSCA and the regulation of renewable chemicals. Ind Biotechnol 8(5):262–271CrossRefGoogle Scholar
  4. Bergeson LL, Auer CM, Hernandez O (2014) Creative adaptation: enhancing oversight of synthetic biology under the toxic substances control act. Ind Biotechnol. doi: 10.1089/ind.2014.1532 Google Scholar
  5. Buschke N, Schafer R, Becker J, Wittmann C (2013) Metabolic engineering of industrial platform microorganisms for biorefinery applications–optimization of substrate spectrum and process robustness by rational and evolutive strategies. Bioresour Technol 135:544–554CrossRefPubMedGoogle Scholar
  6. BusinessWire (2013) Mascoma announces FDA favorable review of its next generation bioengineered yeast, TransFerm Yield+. Accessed 10 Oct 2014
  7. Cao Y, Cao Y, Lin X (2011) Metabolically engineered Escherichia coli for biotechnological production of four-carbon 1,4-dicarboxylic acids. J Ind Microbiol Biotechnol 38(6):649–656CrossRefPubMedGoogle Scholar
  8. Cao Y, Zhang R, Sun C, Cheng T, Liu Y, Xian M (2013) Fermentative succinate production: an emerging technology to replace the traditional petrochemical processes. Biomed Res Int 2013:723412PubMedCentralPubMedGoogle Scholar
  9. Chen Y, Nielsen J (2013) Advances in metabolic pathway and strain engineering paving the way for sustainable production of chemical building blocks. Curr Opin Biotechnol 24(6):965–972CrossRefPubMedGoogle Scholar
  10. Chen C-H, Sassa Y, Suda E, Watanabe KN (2006) Biosafety system frameworks for living modified organisms in Japan and Taiwan. Plant Biotechnol 23(5):539–546. doi: 10.5511/plantbiotechnology.23.539 CrossRefGoogle Scholar
  11. Chen X, Zhou L, Tian K, Kumar A, Singh S, Prior BA, Wang Z (2013) Metabolic engineering of Escherichia coli: a sustainable industrial platform for bio-based chemical production. Biotechnol Adv 31(8):1200–1223CrossRefPubMedGoogle Scholar
  12. Colin VL, Rodriguez A, Cristobal HA (2011) The role of synthetic biology in the design of microbial cell factories for biofuel production. J Biomed Biotechnol 2011:601834PubMedCentralCrossRefPubMedGoogle Scholar
  13. CTNBIO (2014) Commercial approvals: microorganisms. Accessed 22 Oct 2014
  14. Dana GV, Kuiken T, Rejeski D, Snow AA (2012) Synthetic biology: four steps to avoid a synthetic-biology disaster. Nature 483(7387):29CrossRefPubMedGoogle Scholar
  15. Danish K, Epifani LE, Zevin A (2014) Inventory of Federal Regulations Affecting Biofuels other than the Renewable Fuel Standard. VanNess Feldman, LLP. Accessed 16 Oct 2014
  16. Darch H, Shahsavarani A (2012) The regulation of organisms used in agriculture under the Canadian Environmental Protection Act, 1999. In: McHughen A, Wozniak CA (eds) Regulation of agricultural biotechnology: the United States and Canada. Springer, Dordrecht, pp 137–145. doi: 10.1007/978-94-007-2156-2_8 CrossRefGoogle Scholar
  17. Davison J (2005) Risk mitigation of genetically modified bacteria and plants designed for bioremediation. J Ind Microbiol Biotechnol 32(11–12):639–650CrossRefPubMedGoogle Scholar
  18. de Jong B, Siewers V, Nielsen J (2012) Systems biology of yeast: enabling technology for development of cell factories for production of advanced biofuels. Curr Opin Biotechnol 23(4):624–630. doi: 10.1016/j.copbio.2011.11.021 CrossRefPubMedGoogle Scholar
  19. Dellomonaco C, Fava F, Gonzalez R (2010) The path to next generation biofuels: successes and challenges in the era of synthetic biology. Microb Cell Fact 9:3PubMedCentralCrossRefPubMedGoogle Scholar
  20. Eggers B, Mackenzie R (2000) The Cartagena protocol on biosafety. J Int Econ Law 3(3):525–543. doi: 10.1093/jiel/3.3.525 CrossRefGoogle Scholar
  21. Environment Canada (2014) Biotechnology (living organisms) risk assessment decisions. Accessed 22 Oct 2014
  22. Enzing CN, Nooijen A (2012) Algae and genetic modification. Research, production and risks, COGEMGoogle Scholar
  23. European Union (2001) Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the deliberate release into the environment of genetically modified organisms. Accessed 23 Sept 2014
  24. European Union (2009) Directive 2009/41/EC of the European Parliament and of the Council of 6 May 2009 on the contained use of genetically modified micro-organisms. Accessed 23 Sept 2014
  25. Glaser A, Glick P (2012) Growing risk: addressing the invasive potential of bioenergy feedstocks. National Wildlife Federation, Washington, DCGoogle Scholar
  26. Glass DJ (1991) Chapter 10: Impact of government regulation on commercial biotechnology. In: Ono RD (ed) Business of biotechnology, Newnes, Boston, pp 169–198, doi:
  27. Glass DJ (1995) Biotic effects of soil microbial amendments. In: Rechcigl JE (ed) Soil amendments: impacts on biotic systems. Lewis Publishers, Boca Raton, pp 251–303Google Scholar
  28. Glass DJ (2003) Regulation of the commercial uses of microorganisms. In: Encyclopedia of environmental microbiology, Wiley, New York. doi: 10.1002/0471263397.env018
  29. Golden JS, Handfield RB (2014) Why biobased? Opportunities in the emerging bioeconomy. U.S. Department of Agriculture, Accessed 13 Oct 2014
  30. Gressel J, van der Vlugt CJB, Bergmans HEN (2013) Environmental risks of large scale cultivation of microalgae: mitigation of spills. Algal Res 2(3):286–298, 10.1016/j.algal.2013.04.002 CrossRefGoogle Scholar
  31. Gressel J, van der Vlugt CJ, Bergmans HE (2014) Cultivated microalgae spills: hard to predict/easier to mitigate risks. Trends Biotechnol 32(2):65–69. doi: 10.1016/j.tibtech.2013.11.003 CrossRefPubMedGoogle Scholar
  32. Gupta A, Falkner R (2006) The influence of the Cartagena protocol on biosafety: comparing Mexico, China and South Africa. Global Environ Polit 6(4):23–55. doi: 10.1162/glep.2006.6.4.23 CrossRefGoogle Scholar
  33. He MX, Wu B, Qin H, Ruan ZY, Tan FR, Wang JL, Shui ZX, Dai LC, Zhu QL, Pan K, Tang XY, Wang WG, Hu QC (2014) Zymomonas mobilis: a novel platform for future biorefineries. Biotechnol Biofuels 7:101PubMedCentralCrossRefPubMedGoogle Scholar
  34. Henley WJ, Litaker RW, Novoveská L, Duke CS, Quemada HD, Sayre RT (2013) Initial risk assessment of genetically modified (GM) microalgae for commodity-scale biofuel cultivation. Algal Res 2(1):66–77, 10.1016/j.algal.2012.11.001 CrossRefGoogle Scholar
  35. Hong KK, Nielsen J (2012) Metabolic engineering of Saccharomyces cerevisiae: a key cell factory platform for future biorefineries. Cell Mol Life Sci 69(16):2671–2690CrossRefPubMedGoogle Scholar
  36. Jang YS, Park JM, Choi S, Choi YJ, Seung Do Y, Cho JH, Lee SY (2012) Engineering of microorganisms for the production of biofuels and perspectives based on systems metabolic engineering approaches. Biotechnol Adv 30(5)):989–1000CrossRefPubMedGoogle Scholar
  37. Jones CS, Mayfield SP (2012) Algae biofuels: versatility for the future of bioenergy. Curr Opin Biotechnol 23(3):346–351. doi: 10.1016/j.copbio.2011.10.013 CrossRefPubMedGoogle Scholar
  38. Krimsky S (1985) Genetic alchemy: the social history of the recombinant DNA controversy. The MIT Press, Cambridge, MAGoogle Scholar
  39. Kung Y, Runguphan W, Keasling JD (2012) From fields to fuels: recent advances in the microbial production of biofuels. ACS Synth Biol 1(11):498–513. doi: 10.1021/sb300074k CrossRefPubMedGoogle Scholar
  40. Larkum AW, Ross IL, Kruse O, Hankamer B (2012) Selection, breeding and engineering of microalgae for bioenergy and biofuel production. Trends Biotechnol 30(4):198–205. doi: 10.1016/j.tibtech.2011.11.003 CrossRefPubMedGoogle Scholar
  41. Lennen RM, Pfleger BF (2012) Engineering Escherichia coli to synthesize free fatty acids. Trends Biotechnol 30(12):659–667CrossRefPubMedGoogle Scholar
  42. Lennen RM, Pfleger BF (2013) Microbial production of fatty acid-derived fuels and chemicals. Curr Opin Biotechnol 24(6):1044–1053CrossRefPubMedGoogle Scholar
  43. Menetrez MY (2012) An overview of algae biofuel production and potential environmental impact. Environ Sci Technol 46(13):7073–7085. doi: 10.1021/es300917r CrossRefPubMedGoogle Scholar
  44. Nielsen J, Larsson C, van Maris A, Pronk J (2013) Metabolic engineering of yeast for production of fuels and chemicals. Curr Opin Biotechnol 24(3):398–404CrossRefPubMedGoogle Scholar
  45. Nozzi NE, Oliver JW, Atsumi S (2013) Cyanobacteria as a platform for biofuel production. Front Bioeng Biotechnol 1:7PubMedCentralCrossRefPubMedGoogle Scholar
  46. OSTP (1986) Coordinated framework for regulation of biotechnology. Fed Regist 51:23302–23393Google Scholar
  47. Peralta-Yahya PP, Keasling JD (2010) Advanced biofuel production in microbes. Biotechnol J 5(2):147–162CrossRefPubMedGoogle Scholar
  48. Radakovits R, Jinkerson RE, Darzins A, Posewitz MC (2010) Genetic engineering of algae for enhanced biofuel production. Eukaryot Cell 9(4):486–501. doi: 10.1128/ec.00364-09 PubMedCentralCrossRefPubMedGoogle Scholar
  49. Rosenberg JN, Oyler GA, Wilkinson L, Betenbaugh MJ (2008) A green light for engineered algae: redirecting metabolism to fuel a biotechnology revolution. Curr Opin Biotechnol 19(5):430–436. doi: 10.1016/j.copbio.2008.07.008 CrossRefPubMedGoogle Scholar
  50. Rosgaard L, de Porcellinis AJ, Jacobsen JH, Frigaard NU, Sakuragi Y (2012) Bioengineering of carbon fixation, biofuels, and biochemicals in cyanobacteria and plants. J Biotechnol 162(1):134–147. doi: 10.1016/j.jbiotec.2012.05.006 CrossRefPubMedGoogle Scholar
  51. Ryan C (2009) Cultivating clean energy: the promise of algae biofuels. National Resources Defense Council, Washington, DCGoogle Scholar
  52. Sayler GS, Ripp S (2000) Field applications of genetically engineered microorganisms for bioremediation processes. Curr Opin Biotechnol 11(3):286–289CrossRefPubMedGoogle Scholar
  53. Singh JS, Abhilash PC, Singh HB, Singh RP, Singh DP (2011) Genetically engineered bacteria: an emerging tool for environmental remediation and future research perspectives. Gene 480(1–2):1–9CrossRefPubMedGoogle Scholar
  54. Slating TA, Kesan JP (2012) A legal analysis of the effects of the Renewable Fuel Standard (RFS2) and Clean Air Act on the commercialization of biobutanol as a transportation fuel in the United States. GCB Bioenergy 4(2):107–118. doi: 10.1111/j.1757-1707.2011.01146.x CrossRefGoogle Scholar
  55. Snow AA, Smith VH (2012) Genetically engineered algae for biofuels: a key role for ecologists. Bioscience 62(8):765–768. doi: 10.1525/bio.2012.62.8.9 CrossRefGoogle Scholar
  56. Tiedje JM, Colwell RK, Grossman YL, Hodson RE, Lenski RE, Mack RN, Regal PJ (1989) The planned introduction of genetically engineered organisms: ecological considerations and recommendations. Ecology 70(2):298–315CrossRefGoogle Scholar
  57. Trentacoste EM, Martinez AM, Zenk T (2014) The place of algae in agriculture: policies for algal biomass production. Photosynth Res. doi: 10.1007/s11120-014-9985-8 PubMedCentralPubMedGoogle Scholar
  58. Tribe D (2012) Gene technology regulation in Australia: a decade of a federal implementation of a statutory legal code in a context of constituent states taking divergent positions. GM Crops Food: Biotechnol Agric Food Chain 3(1):21–29CrossRefGoogle Scholar
  59. Urgun-Demirtas M, Stark B, Pagilla K (2006) Use of Genetically Engineered Microorganisms (GEMs) for the bioremediation of contaminants. Crit Rev Biotechnol 26(3):145–164. doi: 10.1080/07388550600842794 CrossRefPubMedGoogle Scholar
  60. USDA (1987) Introduction of genetically engineered organisms. Fed Regist 52:22892–22915Google Scholar
  61. USDA (1993) Notification procedures for the introduction of certain regulated articles. Fed Regist 58:17044–17059Google Scholar
  62. USDA (1997) Simplification of requirements and procedures for genetically engineered organisms. Fed Regist 62:23945–23958Google Scholar
  63. USDOE (2010) National algal biofuels technology roadmap. U.S. Dept. of Energy, Office of Energy Efficiency and Renewable Energy, Washington, DCGoogle Scholar
  64. USDOE (2013) Replacing the whole barrel to reduce U.S. dependence on oil. Accessed 20 Oct 2014
  65. USEPA (1997a) Fact sheet: commercialization of Sinorhizobium (Rhizobium) Meliloti, RMBPC-2. Accessed 23 Sept 2014
  66. USEPA (1997b) Microbial products of biotechnology; final regulation under the Toxic Substances Control Act. Fed Regist 62:17910–17958Google Scholar
  67. USEPA (1997c) Points to consider in the preparation of TSCA biotechnology submissions for microorganisms. Accessed 23 Sept 2014
  68. USEPA (1997d) Regulatory impact analysis for the regulation of microbial products of biotechnology: the regulated community. Accessed 23 Sept 2014
  69. USEPA (2012) Microorganisms; general exemptions from reporting requirements; revisions to recipient organisms eligible for tier I and tier II exemptions. Fed Regist 77:54499–54511Google Scholar
  70. USEPA (2014) TSCA Biotechnology notifications, FY 1998 to present. Accessed 23 Oct 2014
  71. USFDA (2014) Generally Recognized as Safe (GRAS) notification program. Accessed 23 Sept 2014
  72. Viebahn M, Smit E, Glandorf DM, Wernars K, Bakker PHM (2009) Effect of genetically modified bacteria on ecosystems and their potential benefits for bioremediation and biocontrol of plant diseases – a review. In: Lichtfouse E (ed) Climate change, intercropping, pest control and beneficial microorganisms, vol 2, Sustainable Agriculture Reviews. Springer, Dordrecht, pp 45–69. doi: 10.1007/978-90-481-2716-0_4 CrossRefGoogle Scholar
  73. Work VH, D’Adamo S, Radakovits R, Jinkerson RE, Posewitz MC (2012) Improving photosynthesis and metabolic networks for the competitive production of phototroph-derived biofuels. Curr Opin Biotechnol 23(3):290–297. doi: 10.1016/j.copbio.2011.11.022 CrossRefPubMedGoogle Scholar
  74. Wozniak C, McClung G, Gagliardi J, Segal M, Matthews K (2012) Regulation of genetically engineered microorganisms under FIFRA, FFDCA and TSCA. In: McHughen A, Wozniak CA (eds) Regulation of agricultural biotechnology: the United States and Canada. Springer, Dordrecht, pp 57–94. doi: 10.1007/978-94-007-2156-2_4 CrossRefGoogle Scholar
  75. Wrubel RP, Krimsky S, Anderson MD (1997) Regulatory oversight of genetically engineered microorganisms: has regulation inhibited innovation? Environ Manage 21(4):571–586CrossRefPubMedGoogle Scholar
  76. Yamanouchi K (2005) Regulatory considerations in the development and application of biotechnology in Japan. Rev Sci Tech 24(1):109–115PubMedGoogle Scholar
  77. Yu C, Cao Y, Zou H, Xian M (2011) Metabolic engineering of Escherichia coli for biotechnological production of high-value organic acids and alcohols. Appl Microbiol Biotechnol 89(3):573–583CrossRefPubMedGoogle Scholar
  78. Zhang F, Rodriguez S, Keasling JD (2011) Metabolic engineering of microbial pathways for advanced biofuels production. Curr Opin Biotechnol 22(6):775–783CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.D. Glass Associates, Inc.NeedhamUSA

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