A review of chimeric proteins/enzymes

Abstract

The low homologous protein chimeric recombination technique by rational design of mutant library proteins in the construction of chimeric esterases by structural domain recombination often produces a large number of inclusion bodies due to misfolding of nascent proteins caused by clashes between residue sidechains, leading to a decrease in soluble protein content. The formation of inclusion bodies is evidence of erroneous interactions of intermediates and the lack of essential cofactors in the cell. Heterotrimeric proteins obtained during chimerisation of low homologous parental chimeric esterases tend to produce misfolding, resulting in inactive chimeric esterases constructed or low soluble protein content. Chimeric enzymes obtained by using structural domain recombination to alter the nature and function of the enzyme play an important role in medicine and industry, among others. Although low homology parental chimerism is more likely to produce chimeric enzymes with new functions, the lower the homology of the parents the more likely it is to produce conflicts between residues, causing the resulting heterotrimeric proteins to misfold and form a large number of inclusion bodies. With the development of bioinformatics technology and improved understanding of protein properties, chimerisation of some low homology protein molecules is now possible. In this article we review several methods and important strategies for directed protein evolution and discuss recent research advances in reducing inclusion bodies to increase soluble protein content.