Skip to main content

Efficient Codon Optimization with Motif Engineering

  • Conference paper
Combinatorial Algorithms (IWOCA 2011)

Part of the book series: Lecture Notes in Computer Science ((LNTCS,volume 7056))

Included in the following conference series:

Abstract

It is now common to add protein coding genes into cloning vectors for expression within non-native host organisms. Codon optimization supports translational efficiency of the desired protein product, by exchanging codons which are rarely found in the host organism with more frequently observed codons. Motif engineering, such as removal of restriction enzyme recognition sites or addition of immuno-stimulatory elements, is also often necessary. We present an algorithm for optimizing codon bias of a gene with respect to a well motivated measure of bias, while simultaneously performing motif engineering. The measure is the previously studied codon adaptation index, which favors the use, in the gene to be optimized, of the most abundant codons found in the host genome. We demonstrate the efficiency and effectiveness of our algorithm on the GENCODE dataset and provide a guarantee that the solution found is always optimal.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aho, A.V.: Algorithms for finding patterns in strings, pp. 255–300. MIT Press, Cambridge (1990)

    MATH  Google Scholar 

  2. Fuglsang, A.: Codon optimizer: a freeware tool for codon optimization. Protein Expression and Purification 31(2), 247–249 (2003)

    Article  Google Scholar 

  3. Gao, W., Rzewski, A., Sun, H., Robbins, P.D., Gambotto, A.: Upgene: Application of a web-based dna codon optimization algorithm. Biotechnology Progress 20(2), 443–448 (2004)

    Article  Google Scholar 

  4. Grote, A., Hiller, K., Scheer, M., Münch, R., Nörtemann, B., Hempel, D.C., Jahn, D.: Jcat: a novel tool to adapt codon usage of a target gene to its potential expression host. Nucleic Acids Research 33(web Server issue), 526–531 (2005)

    Article  Google Scholar 

  5. Gusfield, D.: Algorithms on strings, trees, and sequences. Cambridge Press, New York (1997)

    Book  MATH  Google Scholar 

  6. Gustafsson, C., Govindarajan, S., Minshull, J.: Codon bias and heterologous protein expression. Trends in Biotechnology 22(7), 346–353 (2004)

    Article  Google Scholar 

  7. Holm, L.: Codon usage and gene expression. Nucleic Acids Research 14(7), 3075–3087 (1986)

    Article  Google Scholar 

  8. Hoover, D.M., Lubkowski, J.: Dnaworks: an automated method for designing oligonucleotides for pcr-based gene synthesis. Nucleic Acids Research 30(10), e43 (2002)

    Article  Google Scholar 

  9. Jayaraj, S., Reid, R., Santi, D.V.: Gems: an advanced software package for designing synthetic genes. Nucleic Acids Research 33(9), 3011–3016 (2005)

    Article  Google Scholar 

  10. Kane, J.F.: Effects of rare codon clusters on high-level expression of heterologous proteins in escherichia coli. Current Opinion in Biotechnology 6(5), 494–500 (1995)

    Article  Google Scholar 

  11. Lithwick, G., Margalit, H.: Hierarchy of sequence-dependent features associated with prokaryotic translation. Genome Research 13(12), 2665–2673 (2003)

    Article  Google Scholar 

  12. Puigbo, P., Guzman, E., Romeu, A., Garcia-Vallve, S.: OPTIMIZER: a web server for optimizing the codon usage of DNA sequences. Nucleic Acids Research 35(suppl.2), W126–W131 (2007)

    Article  Google Scholar 

  13. Satya, R.V., Mukherjee, A., Ranga, U.: A pattern matching algorithm for codon optimization and cpg motif-engineering in dna expression vectors. In: CSB 2003: Proceedings of the IEEE Computer Society Conference on Bioinformatics, pp. 294–305. IEEE Computer Society, Washington, DC, USA (2003)

    Google Scholar 

  14. Sharp, P.M., Li, W.H.: The codon adaptation index–a measure of directional synonymous codon usage bias, and its potential applications. Nucleic Acids Research 15(3), 1281–1295 (1987)

    Article  Google Scholar 

  15. The ENCODE Consortium: The ENCODE (ENCyclopedia of DNA elements) project. Science 306(5696), 636–640 (2004)

    Google Scholar 

  16. Varenne, S., Lazdunski, C.: Effect of distribution of unfavourable codons on the maximum rate of gene expression by an heterologous organism. Journal of Theoretical Biology 120(1), 99–110 (1986)

    Article  Google Scholar 

  17. Villalobos, A., Ness, J.E., Gustafsson, C., Minshull, J., Govindarajan, S.: Gene Designer: a synthetic biology tool for constructing artificial DNA segments. BMC Bioinformatics 7, 285 (2006)

    Article  Google Scholar 

  18. Wu, G., Bashir-Bello, N., Freeland, S.J.: The synthetic gene designer: a flexible web platform to explore sequence manipulation for heterologous expression. Protein Expression and Purification 47(2), 441–445 (2006)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Condon, A., Thachuk, C. (2011). Efficient Codon Optimization with Motif Engineering. In: Iliopoulos, C.S., Smyth, W.F. (eds) Combinatorial Algorithms. IWOCA 2011. Lecture Notes in Computer Science, vol 7056. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-25011-8_27

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-25011-8_27

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-25010-1

  • Online ISBN: 978-3-642-25011-8

  • eBook Packages: Computer ScienceComputer Science (R0)

Publish with us

Policies and ethics