Molecular tunnels regulate delivery of substrates/intermediates in enzymes which either harbor deep-seated reaction centers or are for transport of reactive/toxic intermediates that need to be specifically delivered. Here, we focus on the importance of structural diversity in tunnel architectures, especially for the gaseous substrate translocation, in rendering differential substrate preferences and directionality. Two major types of tunnels have been discussed, one that transports stable gases from the environment to the active site, namely, external gaseous (EG) tunnels, and the other that transports molecules between active sites, namely, internal gaseous (IG) tunnels. Aspects as to how the gaseous tunnels have shaped during the course of evolution and their potential to modulate the substrate flow and enzymatic function are examined. In conclusion, the review highlights our perspective on the pulsation mechanism that could facilitate unidirectional translocation of the gaseous molecules through buried tunnels.
© 2021 The Authors. Published by American Chemical Society.