Generation of new protein functions by nonhomologous combinations and rearrangements of domains and modules

Generation of novel protein functions is a major goal in biotechnology and also a rigorous test for our understanding of the relationship between protein structure and function. Early examples of protein engineering focused on design and directed evolution within the constraints of the original protein architecture, exemplified by the highly successful fields of antibody and enzyme engineering. Recent studies show that protein engineering strategies which step away from these natural architectures, that is by manipulating the organization of domains and modules thus mimicking nonhomologous recombination, are highly effective in producing complex and sophisticated functions in terms of both molecular recognition and regulation.