Microbial transglutaminase for biotechnological and biomedical engineering

Research on bacterial transglutaminase dates back to 1989, when the enzyme has been isolated from Streptomyces mobaraensis. Initially discovered during an extensive screening campaign to reduce costs in food manufacturing, it quickly appeared as a robust and versatile tool for biotechnological and pharmaceutical applications due to its excellent activity and simple handling. While pioneering attempts to make use of its extraordinary cross-linking ability resulted in heterogeneous polymers, currently it is applied to site-specifically ligate diverse biomolecules yielding precisely modified hybrid constructs comprising two or more components. This review covers the extensive and rapidly growing field of microbial transglutaminase-mediated bioconjugation with the focus on pharmaceutical research. In addition, engineering of the enzyme by directed evolution and rational design is highlighted. Moreover, cumbersome drawbacks of this technique mainly caused by the enzyme’s substrate indiscrimination are discussed as well as the ways to bypass these limitations.