Codon harmonization - going beyond the speed limit for protein expression

FEBS Lett. 2018 May;592(9):1554-1564. doi: 10.1002/1873-3468.13046. Epub 2018 Apr 16.

Abstract

Codon usage distribution has been soundly used by nature to fine tune protein biogenesis. Alteration of the mRNA structure or sequential scheduling of codons can profoundly affect translation, thus altering protein yield, functionality, solubility, and proper folding. Building on these observations, here, we present an evaluation of different recently designed algorithms of sequence adaptation based on Codon Adaptation Index (CAI) profiling. The first algorithm globally harmonizes synonymous codons in the original sequence in full respect to the heterologous expression host codon usage. The second recodes the sequence in accordance with the native sequence CAI profile. Our data, generated on three model proteins, highlights the importance to consider gene recoding as a parameter itself for recombinant protein expression improvement.

Keywords: Escherichia coli; Codon Adaptation Index; heterologous protein expression; yield improvement.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Base Sequence
  • Codon / genetics*
  • Computational Biology / methods*
  • Gene Expression Regulation*
  • Protein Biosynthesis
  • Solubility

Substances

  • Codon

Associated data

  • GENBANK/KJ807191.1
  • GENBANK/CP000647.1