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

Prates, Erica Teixeira; Crowley, Michael F.; Skaf, Munir S.; Beckham, Gregg T.

doi:10.1021/acs.jpcb.9b06243

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

Journal Article · 04 November 2019 · Journal of Physical Chemistry. B

DOI: https://doi.org/10.1021/acs.jpcb.9b06243 · OSTI ID:1578254

Prates, Erica Teixeira ^[1];

^[2];

^[3];

^[4]

National Renewable Energy Lab. (NREL), Golden, CO (United States). National Bioenergy Center; Univ. of Campinas (UNICAMP), Sao Paulo (Brazil). Inst. of Chemistry and Center for Computing in Engineering and Sciences
National Renewable Energy Lab. (NREL), Golden, CO (United States). Biosciences Center
Univ. of Campinas (UNICAMP), Sao Paulo (Brazil). Inst. of Chemistry and Center for Computing in Engineering and Sciences
National Renewable Energy Lab. (NREL), Golden, CO (United States). National Bioenergy Center

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 in this paper, 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 S_N2-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.

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Research Organization:: National Renewable Energy Laboratory (NREL), Golden, CO (United States)

Sponsoring Organization:: USDOE Office of Energy Efficiency and Renewable Energy (EERE), Bioenergy Technologies Office (EE-3B); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)

Grant/Contract Number:: AC36-08GO28308

OSTI ID:: 1578254

Report Number(s):: NREL/JA--2700-75435

Journal Information:: Journal of Physical Chemistry. B, Journal Name: Journal of Physical Chemistry. B Journal Issue: 48 Vol. 123; ISSN 1520-6106

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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Additional file 2 of Understanding of bacterial lignin extracellular degradation mechanisms by Pseudomonas putida KT2440 via secretomic analysis Xu, Zhangyang; Peng, Bo; Kitata, Reta Birhanu figshare https://doi.org/10.6084/m9.figshare.21443760.v1	dataset	January 2022

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

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