Complex Carbohydrates in Fungal Pathogens and Plant Cell Walls Investigated Using Cellular Solid-State NMR
Complex carbohydrates play crucial roles in energy storage, cell recognition, and structural building. The structure and assembly of cellular polysaccharides are under-investigated compared to proteins and nucleic acids. The technical difficulty is caused by the structural polymorphism and intrinsic disorder of carbohydrate biopolymers when placed in native cellular environments. Here we present our recent progress in using solid-state NMR to investigate the assembly of biomolecules in intact cells, with a focus on carbohydrate structural determination. The current toolbox includes high-field (800-1500 MHz) biomolecular NMR, sensitivity-enhancing Dynamic Nuclear Polarization (DNP) method, database development, and recently, CryoEM technology. We will briefly discuss the findings on a major fungal pathogen named Aspergillus fumigatus, whose cell wall is a heterogeneous composite of glycoproteins, chitin, and diversely linked glucans[2,3]. We have identified a uniquely hydrophobic and stiff cell wall architecture in those fungal cells exposed to echinocandin antifungal drugs and in those mutants devoid of major carbohydrate components. This novel mechanism helps the microbes resist external stresses and retain structural integrity. We will also discuss the structural elucidation of photosynthetic organisms including plants (such as grasses and trees)[4,5] and microalgae. Notably, we have revealed how carbohydrates pack with an aromatic polymer named lignin to form the mechanical core of plant stems. The functions of carbohydrates were found to be conformation-dependent: the hemicellulose xylan uses its non-flat domains to bind lignin and relies on its flat-ribbon domains to coat the even surface of cellulose microfibrils. The in-depth understanding of microbes’ carbohydrate armor and lignocellulose will facilitate the rational development of antifungal drugs and biofuel production technology.
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