Premium
Active Template Synthesis of Protein Heterocatenanes
Author(s) -
Da XiaoDi,
Zhang WenBin
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201904943
Subject(s) - bioconjugation , protein engineering , covalent bond , synthetic biology , chemistry , modular design , macromolecule , denaturation (fissile materials) , combinatorial chemistry , nanotechnology , topology (electrical circuits) , computational biology , materials science , biochemistry , computer science , enzyme , biology , organic chemistry , nuclear chemistry , operating system , mathematics , combinatorics
Covalent‐bond‐forming protein domains can be versatile tools for creating unconventional protein topologies. In this study, through rewiring the SpyTag–SpyCatcher complex to induce rationally designed chain entanglement, we developed a biologically enabled active template for the concise, modular, and programmable synthesis of protein heterocatenanes both in vitro and in vivo. It is a general and good‐yielding reaction for forming heterocatenanes with precisely controlled ring sizes and broad structural diversity. More importantly, such heterocatenation not only provides an efficient means of bioconjugation for integrating multiple native functions, but also enhances the stability of the component proteins against proteolytic digestion, thermal unfolding, and freeze/thaw‐induced mechanical denaturation, thus opening up a versatile path in the nascent field of protein‐topology engineering.