Deciphering molecular mechanisms in Family 7 cellobiohydrolases

Family 7 glycoside hydrolases are among the most important natural cellulase enzymes employed by fungi and other eukaryotes for biomass deconstruction in nature. These enzymes are also currently being used industrially in biomass conversion as major components of fungal cellulase cocktails to produce soluble sugars for upgrading to renewable fuels and chemicals. Given their natural and industrial importance, we are investigating and identifying the molecular features of these enzymes that can be modified for activity enhancements, with an ultimate aim to build structure-activity relationships. This talk will cover several recent investigations where enhanced GH7 cellobiohydrolase activity has been achieved through structural studies based on activity screening of cellulases from natural diversity. Moreover, we have recently examined the role of both N- and O-linked glycosylation on the activity, stability, and binding of the canonical Trichoderma reesei Cel7A cellulase, which has enabled assignment of particular functions to the two glycan classes. Overall, these studies highlight opportunities for engineering these important enzymes for higher activity and stability.