BL21-CodonPlus competent cells are derived from the high-performance Stratagene BL21-Gold competent cell line. These cells enable efficient high-level expression of heterologous proteins in Escherichia coli.

Efficient production of heterologous proteins in E. coli is frequently limited by the rarity of certain tRNAs that are abundant in the organisms from which the heterologous proteins are derived. Forced high-level expression of heterologous proteins can deplete the pool of rare tRNAs and stall translation. BL21-CodonPlus strains are engineered to contain extra copies of genes that encode the tRNAs that most frequently limit translation of heterologous proteins in E. coli. Availability of tRNAs allows high-level expression of many heterologous recombinant genes in BL21-CodonPlus cells that are poorly expressed in conventional BL21 strains.

BL21-CodonPlus-RIL and BL21-CodonPlus(DE3)-RIL cells contain extra copies of the argU, ileY, and leuW tRNA genes. These genes encode tRNAs that recognize the arginine codons AGA and AGG, the isoleucine codon AUA, and the leucine codon CUA, respectively (Table I). The CodonPlus-RIL strains have available the tRNAs that most frequently restrict translation of heterologous proteins from organisms that have AT-rich genomes. BL21-CodonPlus-RP and BL21-CodonPlus(DE3)-RP cells contain extra copies of the argU and proL genes. These genes encode tRNAs that recognize the arginine codons AGA and AGG and the proline codon CCC, respectively. The CodonPlus-RP strains have available the tRNAs that most frequently restrict translation of heterologous proteins of organisms that have GC-rich genomes.  The BL21-CodonPlus (DE3)-RIPL cells contain extra copies of the argU, ileY, and leuW as well as the + tRNA genes. This strain rescues expression of heterologous proteins from organisms that have either AT- or GC-rich genomes.