From experimental observations to a functional model of the lignin pathway: Computational modeling reveals new insights

Abstract

Lignin is a natural polymer that is interwoven with cellulose and hemicellulose within plant cell walls. Due to this molecular arrangement, lignin is a major contributor to the recalcitrance of plant materials with respect to the extraction of sugars and their fermentation into ethanol, butanol, and other potential bioenergy crops. The lignin biosynthetic pathway is similar, but not identical in different plant species. It is in each case comprised of a moderate number of enzymatic steps, but its responses to manipulations, such as gene knock-downs, are complicated by the fact that several of the key enzymes are involved in several reaction steps. This feature poses a challenge to bioenergy production, as it renders it difficult to select the most promising combinations of genetic manipulations for the optimization of lignin composition and amount. Moreover, species specific regulatory features and distinct spatial and topological characteristics hinder accuracy of a unified lignin pathway model. In this dissertation a systems biology approach is used to address these challenges by means of computational modeling. Novel mathematical techniques are employed on different types of experimental data in situ, and shed light on complexities of lignin biosynthesis pathway. The developed methods are nevertheless general enough to be used in a wide range of metabolic modeling applications.