Codon bias and heterologous protein expression

Trends Biotechnol. 2004 Jul;22(7):346-53. doi: 10.1016/j.tibtech.2004.04.006.


The expression of functional proteins in heterologous hosts is a cornerstone of modern biotechnology. Unfortunately, proteins are often difficult to express outside their original context. They might contain codons that are rarely used in the desired host, come from organisms that use non-canonical code or contain expression-limiting regulatory elements within their coding sequence. Improvements in the speed and cost of gene synthesis have facilitated the complete redesign of entire gene sequences to maximize the likelihood of high protein expression. Redesign strategies are discussed here, including modification of translation initiation regions, alteration of mRNA structural elements and use of different codon biases.

Publication types

  • Review

MeSH terms

  • Cloning, Molecular / methods
  • Codon / genetics*
  • Gene Expression Regulation / genetics*
  • Protein Engineering / methods*
  • Proteins / genetics*
  • Recombinant Proteins / biosynthesis*
  • Recombinant Proteins / genetics*
  • Sequence Analysis, DNA / methods*


  • Codon
  • Proteins
  • Recombinant Proteins