Export file:


  • RIS(for EndNote,Reference Manager,ProCite)
  • BibTex
  • Text


  • Citation Only
  • Citation and Abstract

From genetic circuits to industrial-scale biomanufacturing: bacterial promoters as a cornerstone of biotechnology

ChELSI Institute and Advanced Biomanufacturing Centre, Department of Chemical and Biological Engineering, The University of Sheffield, Mappin Street, Sheffield S1 3JD, England

Since the advent of genetic engineering, Escherichia coli, the most widely studied prokaryotic model organism, and other bacterial species have remained at the forefront of biological research. These ubiquitous microorganisms play an essential role in deciphering complex gene regulation mechanisms, large-scale recombinant protein production, and lately the two emerging areas of biotechnology—synthetic biology and metabolic engineering. Among a myriad of factors affecting prokaryotic gene expression, judicious choice of promoter remains one of the most challenging and impactful decisions in many biological experiments. This review provides a comprehensive overview of the current state of bacterial promoter engineering, with an emphasis on its applications in heterologous protein production, synthetic biology and metabolic engineering. In addition to highlighting relevant advances in these fields, the article facilitates the selection of an appropriate promoter by providing pertinent guidelines and explores the development of complementary databases, bioinformatics tools and promoter standardization procedures. The review ends by providing a quick overview of other emerging technologies and future prospects of this vital research area.
  Article Metrics

Keywords promoter engineering; synthetic biology; metabolic engineering; recombinant protein; protein expression; gene regulation; directed evolution

Citation: Pawel Jajesniak, Tuck Seng Wong. From genetic circuits to industrial-scale biomanufacturing: bacterial promoters as a cornerstone of biotechnology. AIMS Bioengineering, 2015, 2(3): 277-296. doi: 10.3934/bioeng.2015.3.277


  • 1. Jacob F, Monod J (1961) Genetic regulatory mechanisms in the synthesis of proteins. J Mol Biol 3: 318-356.    
  • 2. Gorke B, Stulke J (2008) Carbon catabolite repression in bacteria: many ways to make the most out of nutrients. Nat Rev Microbiol 6: 613-624.    
  • 3. Terpe K (2006) Overview of bacterial expression systems for heterologous protein production: from molecular and biochemical fundamentals to commercial systems. Appl Microbiol Biotechnol 72: 211-222.    
  • 4. Weickert MJ, Doherty DH, Best EA, et al. (1996) Optimization of heterologous protein production in Escherichia coli. Curr Opin Biotechnol 7: 494-499.    
  • 5. Blazeck J, Alper HS (2013) Promoter engineering: recent advances in controlling transcription at the most fundamental level. Biotechnol J 8: 46-58.    
  • 6. Busby S, Ebright RH (1994) Promoter structure, promoter recognition, and transcription activation in prokaryotes. Cell 79: 743-746.
  • 7. Hawley DK, McClure WR (1983) Compilation and analysis of Escherichia coli promoter DNA sequences. Nucleic Acids Res 11: 2237-2255.    
  • 8. Harley CB, Reynolds RP (1987) Analysis of E. coli promoter sequences. Nucleic Acids Res 15: 2343-2361.
  • 9. Oliphant AR, Struhl K (1988) Defining the consensus sequences of E.coli promoter elements by random selection. Nucleic Acids Res 16: 7673-7683.
  • 10. Ishihama A (1993) Protein-protein communication within the transcription apparatus. J Bacteriol 175: 2483-2489.
  • 11. Ebright RH, Cossart P, Gicquel-Sanzey B, et al. (1984) Mutations that alter the DNA sequence specificity of the catabolite gene activator protein of E. coli. Nature 311: 232-235.
  • 12. Lewis M, Chang G, Horton NC, et al. (1996) Crystal structure of the lactose operon repressor and its complexes with DNA and inducer. Science 271: 1247-1254.    
  • 13. Monsalve M, Calles B, Mencia M, et al. (1998) Binding of phage phi29 protein p4 to the early A2c promoter: recruitment of a repressor by the RNA polymerase. J Mol Biol 283: 559-569.    
  • 14. Browning DF, Busby SJ (2004) The regulation of bacterial transcription initiation. Nat Rev Microbiol 2: 57-65.    
  • 15. Balleza E, Lopez-Bojorquez LN, Martinez-Antonio A, et al. (2009) Regulation by transcription factors in bacteria: beyond description. FEMS Microbiol Rev 33: 133-151.    
  • 16. Aoyama T, Takanami M, Ohtsuka E, et al. (1983) Essential structure of E. coli promoter: effect of spacer length between the two consensus sequences on promoter function. Nucleic Acids Res 11: 5855-5864.
  • 17. Mulligan ME, Brosius J, McClure WR (1985) Characterization in vitro of the effect of spacer length on the activity of Escherichia coli RNA polymerase at the TAC promoter. J Biol Chem 260: 3529-3538.
  • 18. Jensen PR, Hammer K (1998) The sequence of spacers between the consensus sequences modulates the strength of prokaryotic promoters. Appl Environ Microbiol 64: 82-87.
  • 19. Rud I, Jensen PR, Naterstad K, et al. (2006) A synthetic promoter library for constitutive gene expression in Lactobacillus plantarum. Microbiology 152: 1011-1019.    
  • 20. Alper H, Fischer C, Nevoigt E, et al. (2005) Tuning genetic control through promoter engineering. Proc Natl Acad Sci U S A 102: 12678-12683.    
  • 21. de Boer HA, Comstock LJ, Vasser M (1983) The tac promoter: a functional hybrid derived from the trp and lac promoters. Proc Natl Acad Sci U S A 80: 21-25.    
  • 22. Yansura DG, Henner DJ (1984) Use of the Escherichia coli lac repressor and operator to control gene expression in Bacillus subtilis. Proc Natl Acad Sci U S A 81: 439-443.    
  • 23. Haldimann A, Daniels LL, Wanner BL (1998) Use of new methods for construction of tightly regulated arabinose and rhamnose promoter fusions in studies of the Escherichia coli phosphate regulon. J Bacteriol 180: 1277-1286.
  • 24. Tawfik DS, Griffiths AD (1998) Man-made cell-like compartments for molecular evolution. Nat Biotechnol 16: 652-656.    
  • 25. Yonezawa M, Doi N, Kawahashi Y, et al. (2003) DNA display for in vitro selection of diverse peptide libraries. Nucleic Acids Res 31: e118.    
  • 26. Levy M, Griswold KE, Ellington AD (2005) Direct selection of trans-acting ligase ribozymes by in vitro compartmentalization. RNA 11: 1555-1562.    
  • 27. Ghadessy FJ, Ong JL, Holliger P (2001) Directed evolution of polymerase function by compartmentalized self-replication. Proc Natl Acad Sci U S A 98: 4552-4557.    
  • 28. Griffiths AD, Tawfik DS (2003) Directed evolution of an extremely fast phosphotriesterase by in vitro compartmentalization. EMBO J 22: 24-35.    
  • 29. Griffiths AD, Tawfik DS (2006) Miniaturising the laboratory in emulsion droplets. Trends Biotechnol 24: 395-402.    
  • 30. Sepp A, Choo Y (2005) Cell-free selection of zinc finger DNA-binding proteins using in vitro compartmentalization. J Mol Biol 354: 212-219.    
  • 31. Paul S, Stang A, Lennartz K, et al. (2013) Selection of a T7 promoter mutant with enhanced in vitro activity by a novel multi-copy bead display approach for in vitro evolution. Nucleic Acids Res 41: e29.    
  • 32. Porro D, Gasser B, Fossati T, et al. (2011) Production of recombinant proteins and metabolites in yeasts: when are these systems better than bacterial production systems? Appl Microbiol Biotechnol 89: 939-948.    
  • 33. Berlec A, Strukelj B (2013) Current state and recent advances in biopharmaceutical production in Escherichia coli, yeasts and mammalian cells. J Ind Microbiol Biotechnol 40: 257-274.    
  • 34. Walsh G (2014) Biopharmaceutical benchmarks 2014. Nat Biotechnol 32: 992-1000.    
  • 35. Westers L, Westers H, Quax WJ (2004) Bacillus subtilis as cell factory for pharmaceutical proteins: a biotechnological approach to optimize the host organism. Biochim Biophys Acta 1694: 299-310.    
  • 36. Liu L, Yang H, Shin HD, et al. (2013) How to achieve high-level expression of microbial enzymes: strategies and perspectives. Bioengineered 4: 212-223.    
  • 37. Retallack DM, Jin H, Chew L (2012) Reliable protein production in a Pseudomonas fluorescens expression system. Protein Expr Purif 81: 157-165.    
  • 38. Chen R (2012) Bacterial expression systems for recombinant protein production: E. coli and beyond. Biotechnol Adv 30: 1102-1107.
  • 39. Sorensen HP, Mortensen KK (2005) Advanced genetic strategies for recombinant protein expression in Escherichia coli. J Biotechnol 115: 113-128.    
  • 40. Gopal GJ, Kumar A (2013) Strategies for the production of recombinant protein in Escherichia coli. Protein J 32: 419-425.    
  • 41. Rosano GL, Ceccarelli EA (2014) Recombinant protein expression in Escherichia coli: advances and challenges. Front Microbiol 5: 172.
  • 42. Pan SH, Malcolm BA (2000) Reduced background expression and improved plasmid stability with pET vectors in BL21 (DE3). Biotechniques 29: 1234-1238.
  • 43. Tegel H, Ottosson J, Hober S (2011) Enhancing the protein production levels in Escherichia coli with a strong promoter. FEBS J 278: 729-739.    
  • 44. Balzer S, Kucharova V, Megerle J, et al. (2013) A comparative analysis of the properties of regulated promoter systems commonly used for recombinant gene expression in Escherichia coli. Microb Cell Fact 12: 26.    
  • 45. Gronenborn B (1976) Overproduction of phage lambda repressor under control of the lac promotor of Escherichia coli. Mol Gen Genet 148: 243-250.    
  • 46. Silverstone AE, Arditti RR, Magasanik B (1970) Catabolite-insensitive revertants of lac promoter mutants. Proc Natl Acad Sci U S A 66: 773-779.    
  • 47. Wanner BL, Kodaira R, Neidhardt FC (1977) Physiological regulation of a decontrolled lac operon. J Bacteriol 130: 212-222.
  • 48. Bass SH, Yansura DG (2000) Application of the E. coli trp promoter. Mol Biotechnol 16: 253-260.
  • 49. Somerville RL (1988) The trp promoter of Escherichia coli and its exploitation in the design of efficient protein production systems. Biotechnol Genet Eng Rev 6: 1-41.    
  • 50. Brosius J, Erfle M, Storella J (1985) Spacing of the -10 and -35 regions in the tac promoter. Effect on its in vivo activity. J Biol Chem 260: 3539-3541.
  • 51. Neubauer P, Winter J (2001) Expression and fermentation strategies for recombinant protein production in Escherichia coli. In: Merten OW, Mattanovich D, Lang C et al., editors. Recombinant Protein Production with Prokaryotic and Eukaryotic Cells A Comparative View on Host Physiology. Dordrecht, the Netherlands: Kluwer Academic Publishers; 195-258.
  • 52. Craig SP, 3rd, Yuan L, Kuntz DA, et al. (1991) High level expression in Escherichia coli of soluble, enzymatically active schistosomal hypoxanthine/guanine phosphoribosyltransferase and trypanosomal ornithine decarboxylase. Proc Natl Acad Sci U S A 88: 2500-2504.    
  • 53. Elvin CM, Thompson PR, Argall ME, et al. (1990) Modified bacteriophage lambda promoter vectors for overproduction of proteins in Escherichia coli. Gene 87: 123-126.    
  • 54. Valdez-Cruz NA, Caspeta L, Perez NO, et al. (2010) Production of recombinant proteins in E. coli by the heat inducible expression system based on the phage lambda pL and/or pR promoters. Microb Cell Fact 9: 18.
  • 55. Skerra A (1994) Use of the tetracycline promoter for the tightly regulated production of a murine antibody fragment in Escherichia coli. Gene 151: 131-135.    
  • 56. Guzman LM, Belin D, Carson MJ, et al. (1995) Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter. J Bacteriol 177: 4121-4130.
  • 57. Siegele DA, Hu JC (1997) Gene expression from plasmids containing the araBAD promoter at subsaturating inducer concentrations represents mixed populations. Proc Natl Acad Sci U S A 94: 8168-8172.    
  • 58. Gentz R, Bujard H (1985) Promoters recognized by Escherichia coli RNA polymerase selected by function: highly efficient promoters from bacteriophage T5. J Bacteriol 164: 70-77.
  • 59. Deuschle U, Kammerer W, Gentz R, et al. (1986) Promoters of Escherichia coli: a hierarchy of in vivo strength indicates alternate structures. EMBO J 5: 2987-2994.
  • 60. Samuelson J (2011) Bacterial Systems. In: Robinson AS, editor. Production of Membrane Proteins. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA; 11-35.
  • 61. Studier FW, Moffatt BA (1986) Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes. J Mol Biol 189: 113-130.    
  • 62. Donahue Jr RA, Bebee RL (1999) BL21-SITM competent cells for protein expression in E. coli. Focus 21: 49-51.
  • 63. Lowman HB, Bina M (1990) Temperature-mediated regulation and downstream inducible selection for controlling gene expression from the bacteriophage lambda pL promoter. Gene 96: 133-136.    
  • 64. Studier FW (1991) Use of bacteriophage T7 lysozyme to improve an inducible T7 expression system. J Mol Biol 219: 37-44.    
  • 65. Lee SK, Keasling JD (2005) A propionate-inducible expression system for enteric bacteria. Appl Environ Microbiol 71: 6856-6862.    
  • 66. Choi YJ, Morel L, Le Francois T, et al. (2010) Novel, versatile, and tightly regulated expression system for Escherichia coli strains. Appl Environ Microbiol 76: 5058-5066.    
  • 67. Saida F, Uzan M, Odaert B, et al. (2006) Expression of highly toxic genes in E. coli: special strategies and genetic tools. Curr Protein Pept Sci 7: 47-56.
  • 68. Guan L, Liu Q, Li C, et al. (2013) Development of a Fur-dependent and tightly regulated expression system in Escherichia coli for toxic protein synthesis. BMC Biotechnol 13: 25.    
  • 69. Wu H, Pei J, Jiang Y, et al. (2010) pHsh vectors, a novel expression system of Escherichia coli for the large-scale production of recombinant enzymes. Biotechnol Lett 32: 795-801.    
  • 70. Nocadello S, Swennen EF (2012) The new pLAI (lux regulon based auto-inducible) expression system for recombinant protein production in Escherichia coli. Microb Cell Fact 11: 3.    
  • 71. Bongers RS, Veening JW, Van Wieringen M, et al. (2005) Development and characterization of a subtilin-regulated expression system in Bacillus subtilis: strict control of gene expression by addition of subtilin. Appl Environ Microbiol 71: 8818-8824.    
  • 72. Ming-Ming Y, Wei-Wei Z, Xi-Feng Z, et al. (2006) Construction and characterization of a novel maltose inducible expression vector in Bacillus subtilis. Biotechnol Lett 28: 1713-1718.    
  • 73. Ming YM, Wei ZW, Lin CY, et al. (2010) Development of a Bacillus subtilis expression system using the improved Pglv promoter. Microb Cell Fact 9: 55.    
  • 74. Thuy Le AT, Schumann W (2007) A novel cold-inducible expression system for Bacillus subtilis. Protein Expr Purif 53: 264-269.    
  • 75. Biedendieck R, Gamer M, Jaensch L, et al. (2007) A sucrose-inducible promoter system for the intra- and extracellular protein production in Bacillus megaterium. J Biotechnol 132: 426-430.    
  • 76. Gamer M, Frode D, Biedendieck R, et al. (2009) A T7 RNA polymerase-dependent gene expression system for Bacillus megaterium. Appl Microbiol Biotechnol 82: 1195-1203.    
  • 77. Qiu D, Damron FH, Mima T, et al. (2008) PBAD-based shuttle vectors for functional analysis of toxic and highly regulated genes in Pseudomonas and Burkholderia spp. and other bacteria. Appl Environ Microbiol 74: 7422-7426.    
  • 78. Studier FW (2005) Protein production by auto-induction in high density shaking cultures. Protein Expr Purif 41: 207-234.    
  • 79. Studier FW (2014) Stable expression clones and auto-induction for protein production in E. coli. Methods Mol Biol 1091: 17-32.    
  • 80. Katzen F, Chang G, Kudlicki W (2005) The past, present and future of cell-free protein synthesis. Trends Biotechnol 23: 150-156.    
  • 81. Schwarz D, Dotsch V, Bernhard F (2008) Production of membrane proteins using cell-free expression systems. Proteomics 8: 3933-3946.    
  • 82. Carlson ED, Gan R, Hodgman CE, et al. (2012) Cell-free protein synthesis: applications come of age. Biotechnol Adv 30: 1185-1194.    
  • 83. Guillerez J, Lopez PJ, Proux F, et al. (2005) A mutation in T7 RNA polymerase that facilitates promoter clearance. Proc Natl Acad Sci U S A 102: 5958-5963.    
  • 84. Yadav VG, De Mey M, Lim CG, et al. (2012) The future of metabolic engineering and synthetic biology: towards a systematic practice. Metab Eng 14: 233-241.    
  • 85. Mijakovic I, Petranovic D, Jensen PR (2005) Tunable promoters in systems biology. Curr Opin Biotechnol 16: 329-335.    
  • 86. Pitera DJ, Paddon CJ, Newman JD, et al. (2007) Balancing a heterologous mevalonate pathway for improved isoprenoid production in Escherichia coli. Metab Eng 9: 193-207.    
  • 87. Anthony JR, Anthony LC, Nowroozi F, et al. (2009) Optimization of the mevalonate-based isoprenoid biosynthetic pathway in Escherichia coli for production of the anti-malarial drug precursor amorpha-4,11-diene. Metab Eng 11: 13-19.    
  • 88. Ajikumar PK, Xiao WH, Tyo KE, et al. (2010) Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli. Science 330: 70-74.    
  • 89. Elowitz MB, Leibler S (2000) A synthetic oscillatory network of transcriptional regulators. Nature 403: 335-338.    
  • 90. Gardner TS, Cantor CR, Collins JJ (2000) Construction of a genetic toggle switch in Escherichia coli. Nature 403: 339-342.    
  • 91. Suel GM, Garcia-Ojalvo J, Liberman LM, et al. (2006) An excitable gene regulatory circuit induces transient cellular differentiation. Nature 440: 545-550.    
  • 92. Shetty RP, Endy D, Knight TF, Jr. (2008) Engineering BioBrick vectors from BioBrick parts. J Biol Eng 2: 5.    
  • 93. Radeck J, Kraft K, Bartels J, et al. (2013) The Bacillus BioBrick Box: generation and evaluation of essential genetic building blocks for standardized work with Bacillus subtilis. J Biol Eng 7: 29.    
  • 94. Hershberg R, Bejerano G, Santos-Zavaleta A, et al. (2001) PromEC: An updated database of Escherichia coli mRNA promoters with experimentally identified transcriptional start sites. Nucleic Acids Res 29: 277.    
  • 95. Ishii T, Yoshida K, Terai G, et al. (2001) DBTBS: a database of Bacillus subtilis promoters and transcription factors. Nucleic Acids Res 29: 278-280.    
  • 96. Makita Y, Nakao M, Ogasawara N, et al. (2004) DBTBS: database of transcriptional regulation in Bacillus subtilis and its contribution to comparative genomics. Nucleic Acids Res 32: D75-77.    
  • 97. Sierro N, Makita Y, de Hoon M, et al. (2008) DBTBS: a database of transcriptional regulation in Bacillus subtilis containing upstream intergenic conservation information. Nucleic Acids Res 36: D93-96.    
  • 98. Yao AI, Fenton TA, Owsley K, et al. (2013) Promoter element arising from the fusion of standard BioBrick parts. ACS Synth Biol 2: 111-120.    
  • 99. de Jong A, Pietersma H, Cordes M, et al. (2012) PePPER: a webserver for prediction of prokaryote promoter elements and regulons. BMC Genomics 13: 299.    
  • 100. Klucar L, Stano M, Hajduk M (2010) phiSITE: database of gene regulation in bacteriophages. Nucleic Acids Res 38: D366-370.    
  • 101. Chakravarty A, Carlson JM, Khetani RS, et al. (2007) A novel ensemble learning method for de novo computational identification of DNA binding sites. BMC Bioinformatics 8: 249.    
  • 102. Carlson JM, Chakravarty A, DeZiel CE, et al. (2007) SCOPE: a web server for practical de novo motif discovery. Nucleic Acids Res 35: W259-264.    
  • 103. Czar MJ, Cai Y, Peccoud J (2009) Writing DNA with GenoCAD. Nucleic Acids Res 37: W40-47.    
  • 104. Chandran D, Bergmann FT, Sauro HM (2009) TinkerCell: modular CAD tool for synthetic biology. J Biol Eng 3: 19.    
  • 105. Hill AD, Tomshine JR, Weeding EM, et al. (2008) SynBioSS: the synthetic biology modeling suite. Bioinformatics 24: 2551-2553.    
  • 106. Kaznessis YN (2011) SynBioSS-aided design of synthetic biological constructs. Methods Enzymol 498: 137-152.    
  • 107. Andrianantoandro E, Basu S, Karig DK, et al. (2006) Synthetic biology: new engineering rules for an emerging discipline. Mol Syst Biol2: 2006-0028.
  • 108. Endy D (2005) Foundations for engineering biology. Nature 438: 449-453.    
  • 109. Kelly JR, Rubin AJ, Davis JH, et al. (2009) Measuring the activity of BioBrick promoters using an in vivo reference standard. J Biol Eng 3: 4.    
  • 110. Carrier TA, Keasling JD (1997) Controlling messenger RNA stability in bacteria: strategies for engineering gene expression. Biotechnol Prog 13: 699-708.    
  • 111. Carrier TA, Keasling JD (1999) Library of synthetic 5' secondary structures to manipulate mRNA stability in Escherichia coli. Biotechnol Prog 15: 58-64.    
  • 112. Smolke CD, Carrier TA, Keasling JD (2000) Coordinated, differential expression of two genes through directed mRNA cleavage and stabilization by secondary structures. Appl Environ Microbiol 66: 5399-5405.    
  • 113. Gao X, Yuan XX, Shi ZY, et al. (2012) Production of copolyesters of 3-hydroxybutyrate and medium-chain-length 3-hydroxyalkanoates by E. coli containing an optimized PHA synthase gene. Microb Cell Fact 11: 130.
  • 114. Salis HM, Mirsky EA, Voigt CA (2009) Automated design of synthetic ribosome binding sites to control protein expression. Nat Biotechnol 27: 946-950.    
  • 115. Pfleger BF, Pitera DJ, Smolke CD, et al. (2006) Combinatorial engineering of intergenic regions in operons tunes expression of multiple genes. Nat Biotechnol 24: 1027-1032.    
  • 116. Dueber JE, Wu GC, Malmirchegini GR, et al. (2009) Synthetic protein scaffolds provide modular control over metabolic flux. Nat Biotechnol 27: 753-759.    
  • 117. Topp S, Reynoso CM, Seeliger JC, et al. (2010) Synthetic riboswitches that induce gene expression in diverse bacterial species. Appl Environ Microbiol 76: 7881-7884.    
  • 118. Wang HH, Isaacs FJ, Carr PA, et al. (2009) Programming cells by multiplex genome engineering and accelerated evolution. Nature 460: 894-898.    
  • 119. Warner JR, Reeder PJ, Karimpour-Fard A, et al. (2010) Rapid profiling of a microbial genome using mixtures of barcoded oligonucleotides. Nat Biotechnol 28: 856-862.    


This article has been cited by

  • 1. Hye Jin Lim, Yu Jin Park, Yeon Jae Jang, Ji Eun Choi, Joon Young Oh, Ji Hyun Park, Jae Kwang Song, Dong-Myung Kim, Cell-free synthesis of functional phospholipase A1 from Serratia sp., Biotechnology for Biofuels, 2016, 9, 1, 10.1186/s13068-016-0563-5
  • 2. et al. Engku Alwi, A review of human genome project (HGP) from ethical perspectives, International Journal of ADVANCED AND APPLIED SCIENCES, 2017, 4, 12, 125, 10.21833/ijaas.2017.012.023
  • 3. Shuanghong Zhang, Dingyu Liu, Zhitao Mao, Yufeng Mao, Hongwu Ma, Tao Chen, Xueming Zhao, Zhiwen Wang, Model-based reconstruction of synthetic promoter library in Corynebacterium glutamicum, Biotechnology Letters, 2018, 10.1007/s10529-018-2539-y

Reader Comments

your name: *   your email: *  

Copyright Info: 2015, Tuck Seng Wong, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

Download full text in PDF

Export Citation

Copyright © AIMS Press All Rights Reserved