You want to purify large amounts of a human tumor suppressor protein called Tusu

Question

You want to purify large amounts of a human tumor suppressor protein called Tusup for biochemical studies. The easiest and cheapest way to achieve this is to place the Tusup gene in the bacteria E. coli. Unfortunately, you find that the bacteria produce only a small amount of Tusup. Even worse, they produce far more N-terminal fragments than full-length Tusup proteins. Your advisor notes that your protein has many arginine codons and this may cause a problem. You peruse the literature on codon usage in bacterial and human genes and discover that human genes have a bias for the various arginine codons that differs from that of E. coli genes, as shown in the Table. Why might this different codon usage limit the production of full-length Tusup protein? How might you remedy the problem? (Note: this is a problem experienced by molecular biologists and chem engineers trying to express human proteins in E. coli)

Explanation / Answer

The frequency of arginine codons in Escherichia coli are:

Thus, the Favored Codons in E.coli are: CGT and CGC.

The frequency of arginine codons in Human are:

Thus, the Favored Codons in humans are: CGG, AGA and AGG.

Form the above data, the frequency of arginine codons in E.coli is very high when compared to humans. This change in the frequency of codon limits the full-length production of Tusup protein.   

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