Synthetic and Semisynthetic Metabolic Pathways for Biofuel Production

  • Shikha Bhansali
  • Ashwani Kumar


Recently, metabolic engineering is greatly​ benefited from systems and synthetic biology due to substantial advancements in those fields. The present review aims at importance of metabolic engineering and synthetic biology for production of compounds such as fatty acids, alcohols, and high-value chemicals. The C3 plants, including important food crops like rice, wheat, barley, and soybean overcome RuBisCO’s catalytic inefficiency by enriching some of the traits from algal system. Synthetic and semisynthetic energy conversion systems, based on photosynthetic processes, have recently been proposed. They envisioned that thylakoids with modified PSII can be used outside the living cell in potentially vast amounts and without the requirement of complicated isolation procedures. Another approach could be the use of a native and viable photosynthetic system adapted to serve as a direct source of either sustained electrical current or storable chemical energy and perhaps useful, conduit for electron transport. Balancing and optimization of metabolic engineering and systems biology to develop tailor-made microbial factories for the efficient production of chemicals and biofuels might replace products derived from natural sources in the near future.


Electron transport Photosynthetic process PSII Transmembrane complex 


  1. Agostini F, Voller J-S, Koksch B, Acevedo-Rocha CG, Kubyshkin V, Budisa N (2017) Xenobiology meets enzymology: exploring the potential of unnatural building blocks in biocatalysis. Angew Chem Int Ed Engl,
  2. Ajikumar PK, Xiao W-H, Tyo KEJ, Wang Y, Simeon F, Leonard E, Mucha O, Phon TH, Pfeifer B, Stephanopoulos G (2010) Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli. Science 330:70–74CrossRefGoogle Scholar
  3. Almeida JR, Runquist D, Sanchez i Nogue V, Liden G, Gorwa-Grauslund MF (2011) Stress-related challenges in pentose fermentation to ethanol by the yeast Saccharomyces cerevisiae. Biotechnol J 6:286–299CrossRefGoogle Scholar
  4. Angermayr SA, Hellingwerf KJ, Lindblad P, de Mattos MJ (2009) Energy biotechnology with cyanobacteria. Curr Opin Biotechnol 20:257–263CrossRefGoogle Scholar
  5. Atsumi S, Canna AF, Connora MR, Shena CR, Smitha KM, Brynildsena MP, ChouaKJY HT, Liao JC (2008) Metabolic engineering of Escherichia coli for 1-butanol production. Metab Eng 10:305–311CrossRefGoogle Scholar
  6. Babu RP, O’Connor KO, Seeram R (2013) Current progress on bio-based polymers and their future trends. Prog Biomater 2:1–16CrossRefGoogle Scholar
  7. Barber J (2009) Photosynthetic energy conversion: natural and artificial. Chem Soc Rev 38:185–196CrossRefGoogle Scholar
  8. Becker J, Wittmann C (2016) Systems metabolic engineering of Escherichia coli for the heterologous production of high value molecules a veteran at new shores. Curr Opin Biotechnol 42:178–188CrossRefGoogle Scholar
  9. Beerthuis R, Rothenber G, Shiju NR (2015) Catalytic routes towards acrylic acid, adipic acid and e-caprolactam starting from biorenewables. Green Chem 17:1341–1361CrossRefGoogle Scholar
  10. Bhansali S, Kumar A (2014a) Hairy root culture of Eclipta alba (L.) Hassk J Acad (NY) 4:3–9Google Scholar
  11. Bhansali S, Kumar A (2014b) In vitro production of secondary metabolite using hairy root culture of Eclipta alba (L.) Hassk. Unique J Pharm Biol Sci (UJPBS) 2:97–98Google Scholar
  12. Carroll A, Somerville C (2009) Cellulosic biofuels. Annu Rev Plant Biol 60:165–182CrossRefGoogle Scholar
  13. Case AE, Atsumi S (2016) Cyanobacterial chemical production. J Biotechnol 231:106–114CrossRefGoogle Scholar
  14. Chen JS, Hiu SF (1986) Acetone butanol isopropanol production by Clostridium-Beijerinckii (synonym, clostridium-Butylicum). Biotechnol Lett 8:371–376CrossRefGoogle Scholar
  15. Christianson DW (2008) Unearthing the roots of the terpenome. Curr Opin Chem Biol 12:141–150CrossRefGoogle Scholar
  16. Claypool JT, Ramon DR, Jarboe LR, Nielsen DR (2014) Technoeconomic evaluation of bio-based styrene production by engineered Escherichia coli. J Ind Microbiol Biotechnol 41:1211–1216CrossRefGoogle Scholar
  17. Connor MR, Liao JC (2008) Engineering Escherichia coli for the production of 3-methyl-1-butanol. Appl Environ Microbiol 74:5769–5775CrossRefGoogle Scholar
  18. Dai Z, Nielsen J (2015) Advancing metabolic engineering through systems biology of industrial microorganisms. Curr Opin Biotechnol 36:8–15CrossRefGoogle Scholar
  19. de Jong E, Higson A, Walsh P, Wellisch M (2012) Bio-based chemicals value added products from biorefineries. IEA BioenergyGoogle Scholar
  20. Dismukes GC, Carrieri D, Bennette N, Ananyev GM, Posewitz MC (2008) Aquatic phototrophs: efficient alternatives to land-based crops for biofuels. Curr Opin Biotech 19:235–240CrossRefGoogle Scholar
  21. Dueber JE et al (2009) Synthetic protein scaffolds provide modular control over metabolic flux. Nat Biotechnol 27:753–759CrossRefGoogle Scholar
  22. Erb TJ, Zarzycki J (2016) Biochemical and synthetic biology approaches to improve photosynthetic CO2-fixation. Curr Opin Chem Biol 34:72–79CrossRefGoogle Scholar
  23. Estrela R, Cate JHD (2016) Energy biotechnology in the CRISPR-Cas9 era. Curr Opin Biotechnol 38:79–84CrossRefGoogle Scholar
  24. Feller U, Anders I, Mae T (2008) Rubiscolytics: fate of Rubisco after its enzymatic function in a cell is terminated. J Exp Bot 59:1615–1624CrossRefGoogle Scholar
  25. Gibson DG, Benders GA, Andrews-Pfannkoch C, Denisova EA, Baden-Tillson H, Zaveri J, Stockwell TB, Brownley A, Thomas DW, Algire MA et al (2008) Complete chemical synthesis, assembly, and cloning of a mycoplasma genitalium genome. Science 319:1215–1220CrossRefGoogle Scholar
  26. Giessen TW, Silver PA (2017) Engineering carbon fixation with artificial protein organelles. Curr Opin Biotechnol 46:42–50CrossRefGoogle Scholar
  27. Ha S, Galazka JM, Rin S, Choi J, Yang X, Seo J (2011) Engineered Saccharomyces cerevisiae capable of simultaneous cellobiose and xylose fermentation. Proc Natl Acad Sci U S A 108:504–509CrossRefGoogle Scholar
  28. Hanai T, Atsumi S, Liao JC (2007) Engineered synthetic pathway for isopropanol production in Escherichia coli. Appl Environ Microbiol 73:7814–7818CrossRefGoogle Scholar
  29. Harrison R, Todd P, Rudge S, Petrides D (2015) Bioprocess design and economics. In: Bioseparations science and engineering. Oxford Press, New York. ISBN 978–0–19-539181-7Google Scholar
  30. Jang Y-S, Park JM, Choi S, Choi YJ, Seung DY, Cho JH, Lee SY (2012) Engineering of microorganisms for the production of biofuels and perspectives based on systems metabolic engineering approaches. Biotechnol Adv 30:989–1000CrossRefGoogle Scholar
  31. Jarboe LR, Grabar TB, Yomano LP, Shanmugan KT, Ingram LO (2007) Development of ethanologenic bacteria. Adv Biochem Eng Biotechnol 108:237–261Google Scholar
  32. Jeffries TW (2006) Engineering yeasts for xylose metabolism. Curr Opin Biotechnol 17:320–326CrossRefGoogle Scholar
  33. Jones JA, Toparlak TD, Koffas MAG (2015) Metabolic pathway balancing and its role in the production of biofuels and chemicals. Curr Opin Biotechnol 33:52–59CrossRefGoogle Scholar
  34. Keeling CI, Bohlmann J (2006) Genes, enzymes, and chemicals of terpenoid diversity in the constitutive and induced defense of conifers against insects and pathogens. New Phytol 170:657–675CrossRefGoogle Scholar
  35. Kreel NE, Tabita FR (2015) Serine 363 of a hydrophobic region of archaealribulose 1,5-bisphosphate carboxylase/oxygenase from Archaeoglobusfulgidus and Thermococcuskodakaraensis affects CO2/O2 substrate specificity and oxygen sensitivity. PLoS One 10:e0138351CrossRefGoogle Scholar
  36. Kruse O, Rupprecht J, Mussgnug JH, Dismukes GC, Hankamer B (2005) Photosynthesis: a blueprint for solar energy capture and biohydrogen production technologies. Photochem Photobiol Sci 4:957–970CrossRefGoogle Scholar
  37. Kumar A (2011) Biofuel resources for Green House Gas Mitigation and Environment Protection. In: Trivedi PC (ed) Agriculture biotechnology. Avishkar Publishers, Jaipur, pp 221–246Google Scholar
  38. Kumar A (2013) Biofuels utilisation: an attempt to reduce GHG’s and mitigate climate change. In: Nautiyal S, Kaechele H, Rao KS, Schaldach R (eds) Knowledge systems of societies for adaptation and mitigation of impacts of climate change. Springer-Verlag, Heidelberg, pp 199–224CrossRefGoogle Scholar
  39. Kumar A (2015a) Metabolic engineering in plants. In: Bahadur B, Rajam MV, Sahijram L, Krishnamurthy KV (eds) Plant biology and biotechnology. II Plant genomics and biotechnology. Springer, New Delhi, pp 517–526Google Scholar
  40. Kumar A (2015b) Improving secondary metabolite production in tissue cultures. In: Bahadur B, Rajam MV, Sahijram L, Krishnamurthy KV (eds) Plant biology and biotechnology. II Plant genomics and biotechnology. Springer, New Delhi, pp 397–406Google Scholar
  41. Kumar A, Sharma M, Basu SK, Asif M, Li XP, Chen X (2014) Plant molecular breeding: perspectives from the plant biotechnology and market assisted selection. In: Benkeblia N (ed) Omics technologies and crops improvement. CRC Press, Boca Raton, pp 153–168Google Scholar
  42. Larom S, Salama F, Schuster G, Adir N (2010) Engineering of an alternative electron transfer path in photosystem II. Proc Natl Acad Sci U S A 107:9650–9655CrossRefGoogle Scholar
  43. Lee SK, Chou H, Ham TS, Lee TS, Keasling JD (2008) Metabolic engineering of microorganisms for biofuels production: from bugs to synthetic biology to fuels. Curr Opin Biotechnol 19:556–563CrossRefGoogle Scholar
  44. Leonard E, Kumaran P, Thayer K, Xiao W, Mo JD (2010) Combining metabolic and protein engineering of a terpenoid biosynthetic pathway for overproduction and selectivity control. Proc Natl Acad Sci U S A 107:3654–13659CrossRefGoogle Scholar
  45. Li Y, Horsman M, Wu N, Lan CQ, Dubois-Calero N (2008) Biofuels from microalgae. Biotechnol Prog 24:815–820Google Scholar
  46. Liao JC, Mi L, Pontrelli S, Luo S (2016) Fuelling the future: microbial engineering for the production of sustainable biofuels. Nat Rev Microbiol 14:288–304CrossRefGoogle Scholar
  47. Lindberg P, Park S, Melis A (2009) Engineering a platform for photosynthetic isoprene production in cyanobacteria, using Synechocystis as the model organism. Metab Eng 12:70–79CrossRefGoogle Scholar
  48. Lomoth R et al (2006) Mimicking the electron donor side of photosystem II in artificial photosynthesis. Photosynth Res 87:25–40CrossRefGoogle Scholar
  49. Long SP, Marshall-Colon A, Zhu XG (2015) Meeting the global food demand of the future by engineering crop photosynthesis and yield potential. Cell 161:56–66CrossRefGoogle Scholar
  50. Lynch MD (2016) Into new territory: improved microbial synthesis through engineering of the essential metabolic network. Curr Opin Biotechnol 38:106–111CrossRefGoogle Scholar
  51. Manzanera M, Molina-Munoz ML, Gonzalez-Lopez J (2008) Biodiesel: an alternative fuel. Recent Pat Biotechnol 2:25–34CrossRefGoogle Scholar
  52. Martien JI, Amador-Noguez D (2017) Recent applications of metabolomics to advance microbial biofuel production. Curr Opin Biotechnol 43:118–126CrossRefGoogle Scholar
  53. Meyer MT, McCormick AJ, Griffiths H (2016) Will an algal CO2-concentrating mechanism work in higher plants? Curr Opin Plant Biol 31:181–188CrossRefGoogle Scholar
  54. Neidhardt FC, Curtiss R, Ingraham J, Lin E, Magasanik B, Reznikoff WS, Riley M, Schaechter M, Umbarger HE (1996) Escherichia coli and Salmonella. ASM Press, Washington, DCGoogle Scholar
  55. Nelson N, Yocum CF (2006) Structure and function of photosystems I and II. Annu Rev Plant Biol 57:521–565CrossRefGoogle Scholar
  56. Niehaus TD, Okada S, Devarenne TP, Watt DS, Sviripa V, Chappell J (2011) Identification of unique mechanisms for triterpene biosynthesis in Botryococcus braunii. Proc Natl Acad Sci U S A 108:12260–12265CrossRefGoogle Scholar
  57. O’Connor SE (2015) Engineering of secondary metabolism. Annu Rev Genet 49:71–94CrossRefGoogle Scholar
  58. Parry MA, Andralojc PJ, Scales JC, Salvucci ME, Carmo-Silva AE, Alonso H, Whitney SM (2013) Rubisco activity and regulation as targets for crop improvement. J Exp Bot 64:717–730CrossRefGoogle Scholar
  59. Peter DM, Schada von Borzyskowski L, Kiefer P, Christen P, Vorholt JA, Erb TJ (2015) Screening and engineering the synthetic potential of carboxylating reductases from central metabolism and polyketide biosynthesis. Angew Chem Int Ed Engl 54:13457–13461CrossRefGoogle Scholar
  60. Pitera DJ, Paddon CJ, Newman JD, Keasling JD (2007) Balancing a heterologous mevalonate pathway for improved isoprenoid production in Escherichia coli. Metab Eng 9:193–207CrossRefGoogle Scholar
  61. Sage RF, Stata M (2015) Photosynthetic diversity meets biodiversity: the C4 plant example. J Plant Physiol 172:104–119CrossRefGoogle Scholar
  62. Sanford K, Chotani G, Danielson N, Zahn JA (2016) Scaling up of renewable chemicals. Curr Opin Biotechnol 38:112–122CrossRefGoogle Scholar
  63. Scheffers BR, De Meester L, Bridge TC, Hoffmann AA, Pandolfi JM, Corlett RT, Butchart SH, Pearce-Kelly P, Kovacs KM, Dudgeon D et al (2016) The broad footprint of climate change from genes to biomes to people. Science 354:6313CrossRefGoogle Scholar
  64. Schoondermark-Stolk SA, Jansen M, Veurink JH, Verkleij AJ, Verrips CT, Euverink GJW, Boonstra J, Dijkhuizen L (2006) Rapid identification of target genes for 3-methyl-1-butanol production in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 70:237–246CrossRefGoogle Scholar
  65. Shih PM, Zarzycki J, Niyogi KK, Kerfeld CA (2014) Introduction of a synthetic CO2-fixing photorespiratory bypass into a cyanobacterium. J Biol Chem 289:9493–9500CrossRefGoogle Scholar
  66. Taheripour TMF, Zhuang Q, Tyner WE, Lu X (2012) Biofuels, cropland expansion, and the extensive margin. Energy Sustain Soc 2:25CrossRefGoogle Scholar
  67. Tatsis EC, O’Connor SE (2016) New developments in engineering plant metabolic pathways. Curr Opin Biotechnol 42:126–132CrossRefGoogle Scholar
  68. Tholl D (2006) Terpene synthases and the regulation, diversity and biological roles of terpene metabolism. Curr Opin Plant Biol 9:297–304CrossRefGoogle Scholar
  69. Tyner WE (2012) Biofuels and agriculture: a past perspective and uncertain future. Intl J Sustain Dev World Ecol 19:389–394MathSciNetCrossRefGoogle Scholar
  70. Van Vleet JH, Jeffries TW (2009) Yeast metabolic engineering for hemicellulosic ethanol production. Curr Opin Biotechnol 20:300–306CrossRefGoogle Scholar
  71. Völler J-S, Budisa N (2017) Coupling genetic code expansion and metabolic engineering for synthetic cells. Curr Opin Biotechnol 48:1–7CrossRefGoogle Scholar
  72. Wang J, Guleria S, Koffas MA, Yan Y (2015) Microbial production of value-added nutraceuticals. Curr Opin Biotechnol 37:97–104CrossRefGoogle Scholar
  73. Wang C, Pfleger BF, Kim S (2017) Reassessing Escherichia coli as a cell factory for biofuel production. Curr Opin Biotechnol 45:92–103CrossRefGoogle Scholar
  74. Whitaker WB, Sandoval NR, Bennett RK, Fast AG, Papoutsakis ET (2015) Synthetic methylotrophy: engineering the production of biofuels and chemicals based on the biology of aerobic methanol utilization. Curr Opin Biotechnol 33:165–175CrossRefGoogle Scholar
  75. Wohlbach DJ, Kuo A, Sato TK, Potts KM, Salamov AA, Labutti KM, Sun H (2011) Comparative genomics of xylose-fermenting fungi for enhanced biofuel production. Proc Natl Acad Sci U S A 108:13212–13217CrossRefGoogle Scholar
  76. Woo HM (2017) Solar-to-chemical and solar-to-fuel production from CO2 by metabolically engineered microorganisms. Curr Opin Biotechnol 45:1–7CrossRefGoogle Scholar
  77. Wu J et al (2015) Enhancing flavonoid production by systematically tuning the central metabolic pathways based on a CRISPR interference system in Escherichia coli. Sci Rep 5:13477CrossRefGoogle Scholar
  78. Xu P, Gu Q, Wang W, Wong L, Bower AGW, Collins CH, Koffas MAG (2013) Modular optimization of multi-gene pathways for fatty acids production in E. coli. Nat Commun 4:1409CrossRefGoogle Scholar
  79. Zhu Q, Jackson EN (2015) Metabolic engineering of Yarrowia lipolytica for industrial applications. Curr Opin Biotechnol 36:65–72CrossRefGoogle Scholar

Copyright information

© Springer (India) Pvt. Ltd. 2018

Authors and Affiliations

  1. 1.Department of BotanySS Jain Subodh Girls CollegeSanganer, JaipurIndia
  2. 2.Department of Botany and P.G. School of BiotechnologyUniversity of RajasthanJaipurIndia

Personalised recommendations