LIGNIN-KMC: A Toolkit for Simulating Lignin Biosynthesis

Lignin is an abundant biopolymer of phenylpropanoid monomers that is critical for plant structure and function. Based on the abundance of lignin in the biosphere and interest in lignin valorization, a more comprehensive understanding of lignin biosynthesis is imperative. Here we present an open-source software toolkit, LIGNIN-KMC, that combines kinetic Monte Carlo and first-principles calculations of radical coupling events, which enables modeling of lignin biosynthesis <i>in silico</i>. Specifically, lignification is simulated using the Gillespie algorithm with a graph representation of the lignin fragments and with rates derived from density functional theory calculations of individual fragment couplings. Using this approach, we confirm experimental findings regarding the impact of lignification conditions on final polymer structure and identify new features of fundamental interest to plant cell wall biosynthesis including (1) the monolignol supply rate under <i>in planta</i> lignification conditions likely varies as a function of evolutionary stresses; (2) under conditions of low monolignol supply rates, increasing the fraction of sinapyl alcohol increases the depolymerization yield of monomers upon ether bond cleavage; and (3) by including calculated energetics of caffeyl alcohol homopolymers, the model accurately predicts C-lignin structures. These examples not only highlight the robustness of our modeling framework, but also motivate future studies of new lignin types, unexplored monolignol chemistries, and lignin structure predictions, all with an overarching aim of developing a more comprehensive, molecular understanding of native lignin, which, in turn, can advance the biological and chemistry communities interested in this important biopolymer.