Synthesizing cellulose

Cellulose is the most abundant biomaterial on Earth, yet the mechanism of its synthesis has only begun to be revealed. Understanding cellulose biosynthesis is a significant problem with direct relevance to both glycopolymer sciences and the design of new energy feedstocks with reduced recalcitrance. After decades of research by groups worldwide, an unprecedented discovery was reported in 2013 when the first crystal structure of a bacterial cellulose synthase (Bcs) protein complex was solved.¹ Intriguingly, this multi-domain, membrane-bound Bcs was captured with an intact cellulose chain of 18 glucose units threaded through the binding tunnel in an activated state. From this structure, it is clear that Bcs adds one glucose molecule at a time to the growing cellulose chain from a UDP-glucose donor substrate. After each glucose residue is added to the growing chain, the entire chain must move forward one glucose unit before further elongation. Further details of this processive cycle are unknown. We investigate various scenarios of both the chemical reaction and translocation with advanced molecular simulation methods. The former of these utilizes transition path sampling of hybrid QM/MM (quantum mechanical/molecular mechanical) simulations. These simulations enable the computation of free energy barriers, reveal detailed mechanistic information regarding the glycosyl transfer chemical reaction and cellulose translocation, and aid in elucidating the nature and order of the discrete steps of the synthase processive cycle. This work constitutes the first dynamical look at the method by which the majority of Earth’s organic carbon is produced.

¹J.L. Morgan, J. Strumillo, J. Zimmer, Nature 493, 181 (2013).