Fig 1. Representation of the complementary protein approach.

Two homologous MPs reference protein (blue) and target protein (red) which have high and low (or zero) expression in a selected organism respectively. One can construct chimeric proteins (1^st iteration) comprising parts of the target protein and the reference protein. Analyzing expression yields of the chimeric proteins one can determine which part of the target protein is responsible for a heterologous expression failure. In the next step, one can divide this part of the protein and construct the next chimeric proteins (2^nd iteration). Acting in the same manner one can finally localize the problem of the lack of high yield expression of the target protein (showed as blue star) in a limited number of steps. One can estimate the required number of genetic constructs as 2∙log₂N instead of 2^N point mutations in the case of a random search for the problematic parts of a protein responsible for the failure of the expression, where N is the number of amino acids in the target protein.