Codon usage: Nature's roadmap to expression and folding of proteins

Abstract

Biomedical and biotechnological research relies on processes leading to the successful expression and production of key biological products. High‐quality proteins are required for many purposes, including protein structural and functional studies. Protein expression is the culmination of multistep processes involving regulation at the level of transcription, mRNA turnover, protein translation, and post‐translational modifications leading to the formation of a stable product. Although significant strides have been achieved over the past decade, advances toward integrating genomic and proteomic information are essential, and until such time, many target genes and their products may not be fully realized. Thus, the focus of this review is to provide some experimental support and a brief overview of how codon usage bias has evolved relative to regulating gene expression levels.

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References 108

1. 1.

   Chamary JV, Parmley JL, Hurst LD. Hearing silence: Non-neutral evolution at synonymous sites in mammals. Nat. Rev. Genet. 2006;7:98-108.

   Not in our library10.1038/nrg1770

2. 2.

   Marin M. Folding at the rhythm of the rare codon beat. Biotechnol. J. 2008;3:1047-1057.

   Not in our library10.1002/biot.200800089

3. 3.

   Saunders R, Deane CM. Synonymous codon usage influences the local protein structure observed. Nucleic Acids Res. 2010;38:6719-6728.

   Not in our library10.1093/nar/gkq495

4. 4.

   Plotkin JB, Kudla G. Synonymous but not the same: The causes and consequences of codon bias. Nat. Rev. Genet. 2011;12:32-42.

   Not in our library10.1038/nrg2899

5. 5.

   Zull JE, Smith SK. Is genetic code redundancy related to retention of structural information in both DNA strands? Trends Biochem. Sci. 1990;15:257-261.

   Not in our library10.1016/0968-0004(90)90048-g

6. 6.

   Ikemura T. Correlation between the abundance of Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes: A proposal for a synonymous codon choice that is optimal for the E. coli translational system. J. Mol. Biol. 1981;151:389-409.

   Not in our library10.1016/0022-2836(81)90003-6

7. 7.

   Ikemura T. Codon usage and tRNA content in unicellular and multicellular organisms. Mol. Biol. Evol. 1985;2:13-34.

   Not in our library10.1093/oxfordjournals.molbev.a040335

8. 8.

   Bulmer M. Coevolution of codon usage and transfer RNA abundance. Nature. 1987;325:728-730.

   Not in our library10.1038/325728a0

9. 9.

   Dong H, Nilsson L, Kurland CG. Co-variation of tRNA abundance and codon usage in Escherichia coli at different growth rates. J. Mol. Biol. 1996;260:649-663.

   Not in our library10.1006/jmbi.1996.0428

10. 10.

    Lithwick G, Margalit H. Hierarchy of sequence-dependent features associated with prokaryotic translation. Genome Res. 2003;13:2665-2673.

    Not in our library10.1101/gr.1485203

11. 11.

    Ehrenberg M, Kurland CG. Costs of accuracy determined by a maximal growth rate constraint. Q. Rev. Biophys. 1984;17:45-82.

    Not in our library10.1017/s0033583500005254

12. 12.

    Rocha EP. Codon usage bias from tRNA's point of view: Redundancy, specialization, and efficient decoding for translation optimization. Genome Res. 2004;14:2279-2286.

    Not in our library10.1101/gr.2896904

13. 13.

    Sharp PM, Emery LR, Zeng K. Forces that influence the evolution of codon bias. Philos. Trans. R. Soc., B. 2010;365:1203-1212.

    Not in our library10.1098/rstb.2009.0305

14. 14.

    Duret L. Evolution of synonymous codon usage in metazoans. Curr. Opin. Genet. Dev. 2002;12:640-649.

    Not in our library10.1016/s0959-437x(02)00353-2

15. 15.

    Duret L. tRNA gene number and codon usage in the C. elegans genome are co-adapted for optimal translation of highly expressed genes. Trends Genet. 2000;16:287-289.

    Not in our library10.1016/s0168-9525(00)02041-2

16. 16.

    Plotkin JB, Robins H, Levine AJ. Tissue-specific codon usage and the expression of human genes. Proc. Natl. Acad. Sci. USA. 2004;101:12588-12591.

    Not in our library10.1073/pnas.0404957101

17. 17.

    Semon M, Lobry JR, Duret L. No evidence for tissue-specific adaptation of synonymous codon usage in humans. Mol. Biol. Evol. 2006;23:523-529.

    Not in our library10.1093/molbev/msj053

18. 18.

    Parmley JL, Huynen MA. Clustering of codons with rare cognate tRNAs in human genes suggests an extra level of expression regulation. PLoS Genet. 2009;5:e1000548.

    Not in our library10.1371/journal.pgen.1000548

19. 19.

    Waldman YY, Tuller T, Shlomi T, Sharan R, Ruppin E. Translation efficiency in humans: Tissue specificity, global optimization and differences between developmental stages. Nucleic Acids Res. 2010;38:2964-2974.

    Not in our library10.1093/nar/gkq009

20. 20.

    Ikemura T, Ozeki H. Codon usage and transfer RNA contents: Organism-specific codon-choice patterns in reference to the isoacceptor contents. Cold Spring Harbor Symp. Quant. Biol. 1983;47:1087-1097.

    Not in our library10.1101/sqb.1983.047.01.123

21. 21.

    Bennetzen JL, Hall BD. Codon selection in yeast. J. Biol. Chem. 1982;257:3026-3031.

    Not in our library

22. 22.

    Grantham R, Gautier C, Gouy M, Jacobzone M, Mercier R. Codon catalog usage is a genome strategy modulated for gene expressivity. Nucleic Acids Res. 1981;9:4r3-74.

    Not in our library10.1093/nar/9.1.213-b

23. 23.

    Grosjean H, Fiers W. Preferential codon usage in prokaryotic genes: The optimal codon-anticodon interaction energy and the selective codon usage in efficiently expressed genes. Gene. 1982;18:199-209.

    Not in our library10.1016/0378-1119(82)90157-3

24. 24.

    Gouy M, Gautier C. Codon usage in bacteria: Correlation with gene expressivity. Nucleic Acids Res. 1982;10:7055-7074.

    Not in our library10.1093/nar/10.22.7055

25. 25.

    Kurland CG, Ehrenberg M. Growth-optimizing accuracy of gene expression. Annu. Rev. Biophys. Biophys. Chem. 1987;16:291-317.

    Not in our library10.1146/annurev.bb.16.060187.001451

26. 26.

    Sharp PM, Li WH. The codon Adaptation Index-a measure of directional synonymous codon usage bias, and its potential applications. Nucleic Acids Res. 1987;15:1281-1295.

    Not in our library10.1093/nar/15.3.1281

27. 27.

    Carbone A, Zinovyev A, Kepes F. Codon adaptation index as a measure of dominating codon bias. Bioinformatics. 2003;19:2005-2015.

    Not in our library10.1093/bioinformatics/btg272

28. 28.

    Berg OG, Kurland CG. Growth rate-optimised tRNA abundance and codon usage. J. Mol. Biol. 1997;270:544-550.

    Not in our library10.1006/jmbi.1997.1142

29. 29.

    Moriyama EN, Powell JR. Codon usage bias and tRNA abundance in Drosophila. J. Mol. Evol. 1997;45:514-523.

    Not in our library10.1007/pl00006256

30. 30.

    Powell JR, Moriyama EN. Evolution of codon usage bias in Drosophila. Proc. Natl. Acad. Sci. USA. 1997;94:7784-7790.

    Not in our library10.1073/pnas.94.15.7784

31. 31.

    Stenico M, Lloyd AT, Sharp PM. Codon usage in Caenorhabditis elegans: Delineation of translational selection and mutational biases. Nucleic Acids Res. 1994;22:2437-2446.

    Not in our library10.1093/nar/22.13.2437

32. 32.

    Chiapello H, Lisacek F, Caboche M, Henaut A. Codon usage and gene function are related in sequences of Arabidopsis thaliana. Gene. 1998;209:GC1-GC38.

    Not in our library10.1016/s0378-1119(97)00671-9

33. 33.

    Musto H, Cruveiller S, D'Onofrio G, Romero H, Bernardi G. Translational selection on codon usage in Xenopus laevis. Mol. Biol. Evol. 2001;18:1703-1707.

    Not in our library10.1093/oxfordjournals.molbev.a003958

34. 34.

    Lavner Y, Kotlar D. Codon bias as a factor in regulating expression via translation rate in the human genome. Gene. 2005;345:127-138.

    Not in our library10.1016/j.gene.2004.11.035

35. 35.

    Bernardi G. Isochores and the evolutionary genomics of vertebrates. Gene. 2000;241:3-17.

    Not in our library10.1016/s0378-1119(99)00485-0

36. 36.
    Evidence for selection on synonymous mutations affecting stability of mRNA secondary structure in mammals · 2005

    No notice
37. 37.

    Knight RD, Freeland SJ, Landweber LF. A simple model based on mutation and selection explains trends in codon and amino-acid usage and GC composition within and across genomes. GenomeBiology. 2001;2:research0010-research001013.

    Not in our library10.1186/gb-2001-2-4-research0010

38. 38.
    A General Model of Codon Bias Due to GC Mutational Bias · 2010

    No notice
39. 39.

    Kubo M, Imanaka T. mRNA secondary structure in an open reading frame reduces translation efficiency in Bacillus subtilis. J. Bacteriol. 1989;171:4080-4082.

    Not in our library10.1128/jb.171.7.4080-4082.1989

40. 40.

    de Smit MH, van Duin J. Secondary structure of the ribosome binding site determines translational efficiency: A quantitative analysis. Proc. Natl. Acad. Sci. USA. 1990;87:7668-7672.

    Not in our library10.1073/pnas.87.19.7668

41. 41.

    Tuller T, Carmi A, Vestsigian K, Navon S, et al. An evolutionarily conserved mechanism for controlling the efficiency of protein translation. Cell. 2010;141:344-354.

    Not in our library10.1016/j.cell.2010.03.031

42. 42.
    A Universal Trend of Reduced mRNA Stability near the Translation-Initiation Site in Prokaryotes and Eukaryotes · 2010

    No notice
43. 43.

    Allert M, Cox JC, Hellinga HW. Multifactorial determinants of protein expression in prokaryotic open reading frames. J. Mol. Biol. 2010;402:905-918.

    Not in our library10.1016/j.jmb.2010.08.010

44. 44.

    Kudla G, Murray AW, Tollervey D, Plotkin JB. Coding-sequence determinants of gene expression in Escherichia coli. Science. 2009;324:255-258.

    Not in our library10.1126/science.1170160

45. 45.

    Supek F, Smuc T. On relevance of codon usage to expression of synthetic and natural genes in Escherichia coli. Genetics. 2010;185:1129-1134.

    Not in our library10.1534/genetics.110.115477

46. 46.

    Purvis IJ, Bettany AJ, Santiago TC, Coggins JR, et al. The efficiency of folding of some proteins is increased by controlled rates of translation in vivo. A hypothesis. J. Mol. Biol. 1987;193:413-417.

    Not in our library10.1016/0022-2836(87)90230-0

47. 47.

    Thanaraj TA, Argos P. Protein secondary structural types are differentially coded on messenger RNA. Protein Sci. 1996;5:1973-1983.

    Not in our library10.1002/pro.5560051003

48. 48.

    Wolin SL, Walter P. Ribosome pausing and stacking during translation of a eukaryotic mRNA. EMBO J. 1988;7:3559-3569.

    Not in our library10.1002/j.1460-2075.1988.tb03233.x

49. 49.

    Cortazzo P, Cervenansky C, Marin M, Reiss C, et al. Silent mutations affect in vivo protein folding in Escherichia coli. Biochem. Biophys. Res. Commun. 2002;293:537-541.

    Not in our library10.1016/s0006-291x(02)00226-7

50. 50.

    Komar AA, Lesnik T, Reiss C. Synonymous codon substitutions affect ribosome traffic and protein folding during in vitro translation. FEBS Lett. 1999;462:387-391.

    Not in our library10.1016/s0014-5793(99)01566-5

51. 51.

    Farabaugh PJ. Programmed translational frameshifting. Microbiol. Rev. 1996;60:103-134.

    Not in our library10.1128/mr.60.1.103-134.1996

52. 52.

    Ivanov IP, Atkins JF. Ribosomal frameshifting in decoding antizyme mRNAs from yeast and protists to humans: Close to 300 cases reveal remarkable diversity despite underlying conservation. Nucleic Acids Res. 2007;35:1842-1858.

    Not in our library10.1093/nar/gkm035

53. 53.

    Kimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, et al. A “silent” polymorphism in the MDR1 gene changes substrate specificity. Science. 2007;315:525-528.

    Not in our library10.1126/science.1135308

54. 54.

    Wen JD, Lancaster L, Hodges C, Zeri AC, et al. Following translation by single ribosomes one codon at a time. Nature. 2008;452:598-603.

    Not in our library10.1038/nature06716

55. 55.

    Komar AA. A pause for thought along the co-translational folding pathway. Trends Biochem. Sci. 2009;34:16-24.

    Not in our library10.1016/j.tibs.2008.10.002

56. 56.

    Thangadurai C, Suthakaran P, Barfal P, Anandaraj B, et al. Rare codon priority and its position specificity at the 5' of the gene modulates heterologous protein expression in Escherichia coli. Biochem. Biophys. Res. Commun. 2008;376:647-652.

    Not in our library10.1016/j.bbrc.2008.09.024

57. 57.

    Dittmar KA, Sorensen MA, Elf J, Ehrenberg M, Pan T. Selective charging of tRNA isoacceptors induced by amino-acid starvation. EMBO Rep. 2005;6:151-157.

    Not in our library10.1038/sj.embor.7400341

58. 58.

    Ingolia NT, Ghaemmaghami S, Newman JR, Weissman JS. Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science. 2009;324:218-223.

    Not in our library10.1126/science.1168978

59. 59.

    Fredrick K, Ibba M. How the sequence of a gene can tune its translation. Cell. 2010;141:227-229.

    Not in our library10.1016/j.cell.2010.03.033

60. 60.

    Clarke TF, Clark PL. Increased incidence of rare codon clusters at 5' and 3' gene termini: Implications for function. BMC Genomics. 2010;11:118.

    Not in our library10.1186/1471-2164-11-118

61. 61.

    Darko CA, Angov E, Collins WE, Bergmann-Leitner ES, et al. The clinical-grade 42-kilodalton fragment of merozoite surface protein 1 of Plasmodium falciparum strain FVO expressed in Escherichia coli protects Aotus nancymai against challenge with homologous erythrocytic-stage parasites. Infect. Immun. 2005;73:287-297.

    Not in our library10.1128/iai.73.1.287-297.2005

62. 62.
    Heterologous Protein Expression Is Enhanced by Harmonizing the Codon Usage Frequencies of the Target Gene with those of the Expression Host · 2008

    No notice
63. 63.

    Angov E, Legler PM, Mease RM. Adjustment of codon usage frequencies by codon harmonization improves protein expression and folding. Methods Mol. Biol. 2011;705:1-13.

    Not in our library10.1007/978-1-61737-967-3_1

64. 64.

    Biro JC. Protein folding information in nucleic acids which is not present in the genetic code. Ann. N. Y. Acad. Sci. 2006;1091:399-411.

    Not in our library10.1196/annals.1378.083

65. 65.

    Hamano T, Matsuo K, Hibi Y, Victoriano AF, et al. A single-nucleotide synonymous mutation in the gag gene controlling human immunodeficiency virus type 1 virion production. J. Virol. 2007;81:1528-1533.

    Not in our library10.1128/jvi.01596-06

66. 66.

    Sauna ZE, Kimchi-Sarfaty C, Ambudkar SV, Gottesman MM. Silent polymorphisms speak: How they affect pharmacogenomics and the treatment of cancer. Cancer Res. 2007;67:9609-9612.

    Not in our library10.1158/0008-5472.can-07-2377

67. 67.

    Komar AA. Silent SNPs: Impact on gene function and phenotype. Pharmacogenomics. 2007;8:1075-1080.

    Not in our library10.2217/14622416.8.8.1075

68. 68.

    Komar AA. Genetics. SNPs, silent but not invisible. Science. 2007;315:466-467.

    Not in our library10.1126/science.1138239

69. 69.

    Zhang G, Hubalewska M, Ignatova Z. Transient ribosomal attenuation coordinates protein synthesis and co-translational folding. Nat. Struct. Mol. Biol. 2009;16:274-280.

    Not in our library10.1038/nsmb.1554

70. 70.

    Zhou M, Li X. Analysis of synonymous codon usage patterns in different plant mitochondrial genomes. Mol. Biol. Rep. 2009;36:2039-2046.

    Not in our library10.1007/s11033-008-9414-1

71. 71.

    Makrides SC. Strategies for achieving high-level expression of genes in Escherichia coli. Microbiol. Rev. 1996;60:512-538.

    Not in our library10.1128/mr.60.3.512-538.1996

72. 72.

    Gustafsson C, Govindarajan S, Minshull J. Codon bias and heterologous protein expression. Trends Biotechnol. 2004;22:346-353.

    Not in our library10.1016/j.tibtech.2004.04.006

73. 73.

    Kane JF. Effects of rare codon clusters on high-level expression of heterologous proteins in Escherichia coli. Curr. Opin. Biotechnol. 1995;6:494-500.

    Not in our library10.1016/0958-1669(95)80082-4

74. 74.

    Goldman E, Rosenberg AH, Zubay G, Studier FW. Consecutive low-usage leucine codons block translation only when near the 5' end of a message in Escherichia coli. J. Mol. Biol. 1995;245:467-473.

    Not in our library10.1006/jmbi.1994.0038

75. 75.

    Zhou Z, Schnake P, Xiao L, Lal AA. Enhanced expression of a recombinant malaria candidate vaccine in Escherichia coli by codon optimization. Protein Expression Purif. 2004;34:87-94.

    Not in our library10.1016/j.pep.2003.11.006

76. 76.

    Sorensen HP, Mortensen KK. Advanced genetic strategies for recombinant protein expression in Escherichia coli. J. Biotechnol. 2005;115:113-128.

    Not in our library10.1016/j.jbiotec.2004.08.004

77. 77.

    Brinkmann U, Mattes RE, Buckel P. High-level expression of recombinant genes in Escherichia coli is dependent on the availability of the dnaY gene product. Gene. 1989;85:109-114.

    Not in our library10.1016/0378-1119(89)90470-8

78. 78.

    Cinquin O, Christopherson RI, Menz RI. A hybrid plasmid for expression of toxic malarial proteins in Escherichia coli. Mol. Biochem. Parasitol. 2001;117:245-247.

    Not in our library10.1016/s0166-6851(01)00354-1

79. 79.

    Yu ZB, Jin JP. Removing the regulatory N-terminal domain of cardiac troponin I diminishes incompatibility during bacterial expression. Arch. Biochem. Biophys. 2007;461:138-145.

    Not in our library10.1016/j.abb.2007.01.011

80. 80.

    Rosenberg AH, Goldman E, Dunn JJ, Studier FW, Zubay G. Effects of consecutive AGG codons on translation in Escherichia coli, demonstrated with a versatile codon test system. J. Bacteriol. 1993;175:716-722.

    Not in our library10.1128/jb.175.3.716-722.1993

81. 81.

    Thanaraj TA, Argos P. Ribosome-mediated translational pause and protein domain organization. Protein Sci. 1996;5:1594-1612.

    Not in our library10.1002/pro.5560050814

82. 82.

    Hillier CJ, Ware LA, Barbosa A, Angov E, et al. Process development and analysis of liver-stage antigen 1, a preerythrocyte-stage protein-based vaccine for Plasmodium falciparum. Infect. Immun. 2005;73:2109-2115.

    Not in our library10.1128/iai.73.4.2109-2115.2005

83. 83.

    Chowdhury DR, Angov E, Kariuki T, Kumar N. A potent malaria transmission blocking vaccine based on codon harmonized full length Pfs48/45 expressed in Escherichia coli. PLoS One. 2009;4:e6352.

    Not in our library10.1371/journal.pone.0006352

84. 84.

    Francis DM, Page R. Strategies to optimize protein expression in E. coli. Current Protocols in Protein Science. 2010.

    Not in our library10.1002/0471140864.ps0524s61

85. 85.

    Murasugi A. Secretory expression of human protein in the Yeast Pichia pastoris by controlled fermentor culture. Recent Pat. Biotechnol. 2010;4:153-166.

    Not in our library10.2174/187220810791110679

86. 86.

    Trowitzsch S, Bieniossek C, Nie Y, Garzoni F, Berger I. New baculovirus expression tools for recombinant protein complex production. J. Struct. Biol. 2010;172:45-54.

    Not in our library10.1016/j.jsb.2010.02.010

87. 87.

    Idiris A, Tohda H, Kumagai H, Takegawa K. Engineering of protein secretion in yeast: Strategies and impact on protein production. Appl. Microbiol. Biotechnol. 2010;86:403-417.

    Not in our library10.1007/s00253-010-2447-0

88. 88.

    Desai PN, Shrivastava N, Padh H. Production of heterologous proteins in plants: Strategies for optimal expression. Biotechnol. Adv. 2010;28:427-435.

    Not in our library10.1016/j.biotechadv.2010.01.005

89. 89.

    Burgess-Brown NA, Sharma S, Sobott F, Loenarz C, et al. Codon optimization can improve expression of human genes in Escherichia coli: A multi-gene study. Protein Expression Purif. 2008;59:94-102.

    Not in our library10.1016/j.pep.2008.01.008

90. 90.

    Sahdev S, Khattar SK, Saini KS. Production of active eukaryotic proteins through bacterial expression systems: A review of the existing biotechnology strategies. Mol. Cell. Biochem. 2008;307:249-264.

    Not in our library10.1007/s11010-007-9603-6

91. 91.

    Peti W, Page R. Strategies to maximize heterologous protein expression in Escherichia coli with minimal cost. Protein Expression Purif. 2007;51:1-10.

    Not in our library10.1016/j.pep.2006.06.024

92. 92.

    Terpe K. Overview of bacterial expression systems for heterologous protein production: From molecular and biochemical fundamentals to commercial systems. Appl. Microbiol. Biotechnol. 2006;72:211-222.

    Not in our library10.1007/s00253-006-0465-8

93. 93.

    Berisio R, Schluenzen F, Harms J, Bashan A, et al. Structural insight into the role of the ribosomal tunnel in cellular regulation. Nat. Struct. Biol. 2003;10:366-370.

    Not in our library10.1038/nsb915

94. 94.

    Varenne S, Buc J, Lloubes R, Lazdunski C. Translation is a non-uniform process. Effect of tRNA availability on the rate of elongation of nascent polypeptide chains. J. Mol. Biol. 1984;180:549-576.

    Not in our library10.1016/0022-2836(84)90027-5

95. 95.

    Lu J, Deutsch C. Folding zones inside the ribosomal exit tunnel. Nat. Struct. Mol. Biol. 2005;12:1123-1129.

    Not in our library10.1038/nsmb1021

96. 96.

    Kramer G, Boehringer D, Ban N, Bukau B. The ribosome as a platform for co-translational processing, folding and targeting of newly synthesized proteins. Nat. Struct. Mol. Biol. 2009;16:589-597.

    Not in our library10.1038/nsmb.1614

97. 97.

    Lu J, Kobertz WR, Deutsch C. Mapping the electrostatic potential within the ribosomal exit tunnel. J. Mol. Biol. 2007;371:1378-1391.

    Not in our library10.1016/j.jmb.2007.06.038

98. 98.

    Lu J, Deutsch C. Electrostatics in the ribosomal tunnel modulate chain elongation rates. J. Mol. Biol. 2008;384:73-86.

    Not in our library10.1016/j.jmb.2008.08.089

99. 99.

    Voges D, Watzele M, Nemetz C, Wizemann S, Buchberger B. Analyzing and enhancing mRNA translational efficiency in an Escherichia coli in vitro expression system. Biochem. Biophys. Res. Commun. 2004;318:601-614.

    Not in our library10.1016/j.bbrc.2004.04.064

100. 100.

     Lorimer D, Raymond A, Walchli J, Mixon M, et al. Gene composer: Database software for protein construct design, codon engineering, and gene synthesis. BMC Biotechnol. 2009;9:36.

     Not in our library10.1186/1472-6750-9-36

101. 101.

     Sandhu KS, Pandey S, Maiti S, Pillai B. GASCO: Genetic algorithm simulation for codon optimization. In Silico Biol. 2008;8:187-192.

     Not in our library

102. 102.

     Cai Y, Sun J, Wang J, Ding Y, et al. Optimizing the codon usage of synthetic gene with QPSO algorithm. J. Theor. Biol. 2008;254:123-127.

     Not in our library10.1016/j.jtbi.2008.05.010

103. 103.

     Puigbo P, Guzman E, Romeu A, Carcia-Vallve S. OPTIMIZER: A web server for optimizing the codon usage of DNA squences. Nucleic Acids Res. 2007;35:W126-W131.

     Not in our library10.1093/nar/gkm219

104. 104.
     Gene Designer: a synthetic biology tool for constructing artificial DNA segments · 2006

     No notice
105. 105.

     Wu G, Bashir-Bello N, Freeland SJ. The synthetic gene designer: A flexible web platform to explore sequence manipulation for heterologous expression. Protein Expression Purif. 2006;47:441-445.

     Not in our library10.1016/j.pep.2005.10.020

106. 106.

     Grote A, Hiller K, Scheer M, Munch R, et al. JCat: A novel tool to adapt codon usage of a target gene to its potential expression host. Nucleic Acids Res. 2005;33:W526-531.

     Not in our library10.1093/nar/gki376

107. 107.

     Jayaraj S, Reid R, Santi DV. GeMS: An advanced software package for designing synthetic genes. Nucleic Acids Res. 2005;33:3011-3016.

     Not in our library10.1093/nar/gki614

108. 108.

     Gao W, Rzewski A, Sun H, Robbins PD, Gambotto A. UpGene: Application of a web-based DNA codon optimization algorithm. Biotechnol. Prog. 2004;20:443-448.

     Not in our library10.1021/bp0300467

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