What if the protein can't be expressed and purified in E. coli system?

Today, I saw an interesting question to share with you here.

What if the protein can't be expressed and purified in E. coli system?

Here are a few things can be done to solve the problem:

(1) codon optimization is recommended if it has not been;

(2) remove the transmembrane region and signal peptide region;

(3) try to express truncated domains of the protein;

(4) try different tags to increase the expression level;

(5) try different expression systems (e.g. insect cell system for certain proteins).

You can find more information about protein expression here.