Catalytic Mechanism of Aryl-Ether Bond Cleavage in Lignin by LigF and LigG

Michael Crowley, Erica Prates, Gregg Beckham, Munir Skaf

Research output: Contribution to journalArticlepeer-review

5 Scopus Citations


Given the abundance of lignin in nature, multiple enzyme systems have been discovered to cleave the β-O-4 bonds, the most prevalent intermonomer linkage. In particular, stereospecific cleavage of lignin oligomers by glutathione S-transferases (GSTs) has been reported in several sphingomonads. Here, we apply quantum mechanics/molecular mechanics simulations to study the mechanism of two glutathione-dependent enzymes in the β-aryl ether catabolic pathway of Sphingomonas sp. SYK-6, namely, LigF, a β-etherase, and LigG, a lyase. For LigF, the free-energy landscape supports a SN2 reaction mechanism, with the monoaromatic leaving group being promptly neutralized upon release. Specific interactions with conserved residues are responsible for stereoselectivity and for activation of the cofactor as a nucleophile. A glutathione conjugate is also released by LigF and serves the substrate of LigG, undergoing a SN2-like reaction, in which Cys15 acts as the nucleophile, to yield the second monoaromatic product. The simulations suggest that the electron-donating substituent at the para-position found in lignin-derived aromatics and the interaction with Tyr217 are essential for reactivity in LigG. Overall, this work deepens the understanding of the stereospecific enzymatic mechanisms in the β-aryl ether cleavage pathway and reveals key structural features underpinning the ligninolytic activity detected in several sphingomonad GSTs.

Original languageAmerican English
Pages (from-to)10142-10151
Number of pages10
JournalJournal of Physical Chemistry B
Issue number48
StatePublished - 5 Dec 2019

Bibliographical note

Publisher Copyright:
Copyright © 2019 American Chemical Society.

NREL Publication Number

  • NREL/JA-2800-75435


  • BCPL
  • enzyme
  • lignin
  • mechanism
  • molecular modeling
  • qmmm


Dive into the research topics of 'Catalytic Mechanism of Aryl-Ether Bond Cleavage in Lignin by LigF and LigG'. Together they form a unique fingerprint.

Cite this