IsoLife – Stable Isotope Labelled Plant Products for the Life Sciences

Applications  |  Biotechnology: Detailed chemical structure analysis by NMR

Solid-state selective NMR to resolves 3D structure of plant and fungal cell walls

Introduction

The chemical structure of plant cell walls is a complex matrix of lignin and hemicellulose that supports the cellulose fiber bundles. This molecular cell wall architecture is still largely ‘terra incognita’, but can be effectively studied using solid-state NMR (Foston et al, 2012a; Komatsu and Kikuchi, 2013a; Dupree et al, 2015; Kang et al, 2019). The close interaction between the structural elements of cell walls makes biological degradation difficult (‘recalcitrance’; Foston et al, 2012b; 2015).

 

Figure 1. Hemicellulosic signals of lignocellulosic mixtures for revealing the supramolecular structure of lignocellulose obtained by solid-state dipolar dephasing filtered (DDF)-INADEQUATE 2D experiments (Komatsu & Kikuchi, 2013a)

It is important to unravel the plant cell wall structure and its capability to resist enzymatic degradation e.g. to improve conversion technologies for biofuel production (Ragauskas et al, 2006; Terrett et al, 2019). Moreover, new fundamental knowledge of the fungal cell wall molecular architecture helps to find new selective fungicides and antibiotics against antibiotic-resistant pathogenic fungi (Kang et al, 2018).

 

Figure 2. a) Possible models of the molecular architecture of softwood. The ratio of polysaccharide chains is based on the integrals of carbon 4–6 (carbon 4–5 for xylan) cross-peaks in the 30 ms CP-PDSD MAS NMR spectrum and the monosaccharide analysis. Lignin is shown mostly associated with itself, but is close to galactoglucomannan, xylan and domain 2 cellulose.
b) Model of spruce cell wall macrofibril. Groups of cellulose microfibrils with bound GGM and xylan form macrofibrils in spruce cell walls. Lignin is localised to the surface of the polysaccharide core of the macrofibril (Terrett et al. 2019).

Stable Isotope Solution: Solid State 13C Excitation and Spin Diffusion NMR

Cellulose is a polysaccharide consisting of a linear chain of β(1→4)-linked D-glucose units packed in both crystalline and amorphous structures in the cell wall. Hemicellulose also occurs in most cell walls and contains branched polymers such as arabinoxylans. Lignin, a complex, highly heterogeneous aromatic polymer composed of hydroxycinnamyl monomers with various degrees of methoxylation, is the third important cell wall constituent. The close interaction between the three polymers determines the resistence to enzymatic degradation. A common method to reduce this resistence is a thermochemical pretreatment, an acid hydrolysis at 180oC that removes hemicellulose, disrupts the lignin structure, and enhances degradation of cellulose (Kumar et al, 2009). Solid-state NMR spin diffusion (13C CP/MAS and SELDOM) is a particularly useful tool to determine the changes by this pretreatment by measuring inter- and intramacromolecular distances in cell walls of tissues, like 13C labelled corn stover obtained from IsoLife (Foston et al, 2012a; 2015).

Results from publications with IsoLife’s products

Foston et al (2012a) conclude that hemicellulose, which was removed in the pretreated sample by acid hydrolysis, lies at the interface between lignin and cellulose. The authors believe that a major mechanism of pretreatment – the removal of the hemicellulose layer -, disrupts the hemicellulose−lignin matrix in the plant cell wall, thus reducing the recalcitrance against enzymatic degradation of cellulose (Foston et al, 2012a).

In a follow-up paper, Foston et al (2012b) used 13C ionic liquid NMR to accurately and rapidly measure plant cell wall composition. The 13C spectral S/N ratio obtained for natural abundant corn stover (Figure 3) was about one-fourth that of the 13C enriched corn stover, yet requiring a 216 times longer data acquisition period. Even at long acquisition time, the spectrum of the natural abundant corn stover lacks the detail for analyzing any significant cell wall chemistry and is dominated by solvent peaks.

The authors conclude that the results suggest that lignin is in close contact with both hemicellulose and cellulose. The 13C CP SELDOM spin diffusion measurements on the pretreated 13C corn stover did not indicate that significant magnetization transfer between the lignin and the cellulose occured even at the longest mixing time. This seems to confirm that hemicellulose, which was removed in the pretreated sample by acid hydrolysis, lies at the interface between lignin and cellulose. The authors believe that a major mechanisms of pretreatment – the removal of the hemicellulose layer -, disrupts the hemicellulose−lignin matrix in the plant cell wall, thus reducing the resistance against enzymatic degradation of cellulose (Foston et al, 2012a).

In their next publication, Foston et al. (2012b) used 13C ionic liquid NMR to accurately and rapidly measure plant cell wall composition. The 13C spectral S/N ratio obtained for natural abundant corn stover (Figure 3) was about one-fourth that of the13C enriched corn stover, yet requiring a 216 times longer data acquisition period. Even at long acquisition time, the spectrum of the natural abundant corn stover lacks the detail for analyzing any significant cell wall chemistry and is dominated by solvent peaks.

Figure 3. Stacked plot of 13C spectra of 13C enriched and control natural abundant corn stover stem samples in a deuterated ionic liquid–DMSO mixture. Peaks at d127.5, 146.4 and 141.4 ppm are from pyridinium chloride and d39.5 ppm belongs to DMSO.

With regard to measuring time, the results indicate that uniformly 13C enriched (>97 atom %) plant materials permit high throughput NMR-analyses by reducing the experimental times by 50 (Johnson & Schmidt-Rohr, 2014) up to ~220 fold (Foston et al. 2012b). Another conclusion, highly important with respect to the use of 13C labeling, is that 13C incorporation caused no gross changes in cell wall chemistry.

Applications in various fields demonstrate the utility of 13C enrichment, including: CMP-NMR for food chemistry (Lam et al, 2014);

  • Comparison of dicot and monocot lignocellulose structure (Komatsu and Kikuchi, 2013b);
  • Fire resistance of cellulosic materials (Bücker et al, 2014; REDOR NMR);
  • Structure analysis of amino acid-derivatives, plant matter, chars from low-temperature pyrolysis, and humic acid (Johnson & Schmidt-Rohr, 2014; Multi-CP NMR).
  • Using EXPANSE and DQ/SQ NMR spectroscopy, Chen et al (2020) – for the first time – identified fused-ring aromatics formed during the aerobic decomposition of wheat (Triticum sp.) straw in soil, concluding that the observed formation of polyaromatic units as plant litter decomposes provides direct evidence for humification.
  • Fortier-McGill et al (2017) monitored molecular fluxes and changes in cell walls of germinating wheat seeds and growing seedlings during 4 days, by CMP-NMR, i.e. in all phases, liquid, gel-like, semisolid, and solid.

References

Bücker M, C Jäger, D Pfeifer, B Unger. 2014.
Evidence of Si–O–C bonds in cellulosic materials modified by sol–gel-derived silica.
Wood Science Technology 48: 1033-1047.

Chen X, X Ye, W Chu, DC Olk, X Cao, K Schmidt-Rohr, L Zhang, ML Thompson, J Mao, H Gao. 2020.
Formation of char-like, fused-ring aromatic structures from a nonpyrogenic pathway during decomposition of wheat straw.
Journal of Agricultural and Food Chemistry 68: 2607-2614.

Dupree R, TJ Simmons, J Mortimer, D Patel, D Iuga, SP Brown, P Dupree. 2015.
Probing the molecular architecture of Arabidopsis thaliana secondary cell walls using two- and three-dimensional 13C solid-state NMR spectroscopy.
Biochemistry 54: 2335-2345.

Fortier-McGill B, RD Majumdar, L Lam, R Soong, YL Mobarhan, A Sutrisno, R de Visser, MJ Simpson, H Wheeler, M Campbell, A Gorissen, AJ Simpson. 2017.
Comprehensive multiphase (CMP) NMR monitoring of the structural changes and molecular flux within a growing seed.
Journal of Agricultural and Food Chemistry: 65: 6779–6788.

Foston M, R Katahira, E Gjersing, MF Davis, AJ Ragauskas. 2012a.
Solid-state selective 13C excitation and spin diffusion NMR to resolve spatial dimensions in plant cell walls.
Journal of Agricultural and Food Chemistry 60: 1419-1427.

Foston M, R Samuel, AJ Ragauskas. 2012.
13C cell wall enrichment and ionic liquid NMR analysis: progress towards a high-throughput detailed chemical analysis of the whole plant cell wall.
Analyst 137: 3904-3909.

Johnson RL, K Schmidt-Rohr. 2014.
Quantitative solid-state 13C NMR with signal enhancement by multiple cross polarization.
Journal of Magnetic Resonance 239: 44-49.

Kang X, A Kirui, MC Dickwella Widanage, F Mentink-Vigier, DJ Cosgrove, T Wang. 2019.
Lignin-polysaccharide interactions in plant secondary cell walls revealed by solid-state NMR.
NATURE Communications 10: 347.

Kang X, A Kirui, A Muszyński, MC Dickwella Widanage, A Chen, P Azadi, P Wang, F Mentink-Vigier, T Wang. 2018.
Molecular architecture of fungal cell walls revealed by solid-state NMR.
NATURE Communications 9: 2747.

Komatsu T, J Kikuchi. 2013.
Selective signal detection in solid-state NMR using rotor-synchronized dipolar dephasing for the analysis of hemicellulose in lignocellulosic biomass.
The Journal of Physical Chemistry Letters 4: 2279−2283

Kumar P, D Barrett, M Delwiche, P Stroeve. 2009.
Methods for pretreatment of lignocellulosic biomass for efficient hydrolysis and biofuel production.
Industrial & Engineering Chemistry Research 48: 3713−3729.

Lam L, R Soong, A Sutrisno, R de Visser, MJ Simpson, H Wheeler, M Campbell, WE Maas, M Fey, A Gorissen, H Hutchins, B Andrew, JO Struppe, S Krishnamurthy, R Kumar, M Monette, H Stronks, A Hume, AJ Simpson. 2014.
Comprehensive multiphase NMR spectroscopy of intact 13C labeled seeds.
Journal of Agricultural and Food Chemistry 62: 407-415.

Ragauskas AJ, CK Williams, BH Davison, G Britovsek. 2006.
The Path Forward for Biofuels and Biomaterials..
Science 311: 484−489.

Terrett OM, JJ Lyczakowski, L Yu, D Luga, WT Franks, SP Brown, R Dupree, P Dupree. 2019.
Molecular architecture of softwood revealed by solid-state NMR.
NATURE Communications 10: 4978.