Effects of rare codon clusters on high-level expression of heterologous proteins in Escherichia coli

Curr Opin Biotechnol. 1995 Oct;6(5):494-500. doi: 10.1016/0958-1669(95)80082-4.


Within Escherichia coli and other species, a clear codon bias exists among the 61 amino acid codons found within the population of mRNA molecules, and the level of cognate tRNA appears directly proportional to the frequency of codon usage. Given this situation, one would predict translational problems with an abundant mRNA species containing an excess of rare low tRNA codons. Such a situation might arise after the initiation of transcription of a cloned heterologous gene in the E. coli host. Recent studies suggest clusters of AGG/AGA, CUA, AUA, CGA or CCC codons can reduce both the quantity and quality of the synthesized protein. In addition, it is likely that an excess of any of these codons, even without clusters, could create translational problems.

Publication types

  • Review

MeSH terms

  • Arginine
  • Base Sequence
  • Codon*
  • Escherichia coli / genetics*
  • Gene Expression
  • Molecular Sequence Data
  • Multigene Family
  • Mutation
  • Protein Biosynthesis*
  • Recombinant Proteins / biosynthesis*
  • Ribosomes


  • Codon
  • Recombinant Proteins
  • Arginine