Hyperthermophilic xylanase and thermophilicity analysis by molecular dynamic simulation with quantum mechanics

Appl Microbiol Biotechnol. 2024 Dec 4;108(1):526. doi: 10.1007/s00253-024-13356-3.

Abstract

Thermophilic xylanases catalyzing the cleavage of β-1,4-glycosidic bonds in xylan have applications in food, feed, biorefinery, and pulp industries. In this study, a hyperthermophilic endo-xylanase was obtained by further enhancement of thermal tolerance of a thermophilic GH11 xylanase originated from metagenome of bagasse pile based on rational design. Introducing N13F and Q34L to the previously reported X11P enzyme shifted the optimal working temperature to 85 °C and led to 20.7-fold improvement in thermostability at 90 °C along with a marked increase in Tm to 93.3 °C. X11PNQ enzyme converted xylan to prebiotic xylooligosaccharides with high specificity on xylobiose to xylohexaose and high operational stability at 85 °C, resulting in 10.3-folds yield improvement compared to the parental enzyme. Molecular dynamic simulation and quantum mechanical analysis revealed improved H-bonding networks within GH11 xylanase principal domains and greater dynamic cross-correlations. A novel thermostabilization mechanism by π-amide interaction with slightly lower interaction energy than the native H-bond, but compensated by increased occurrence frequency was firstly demonstrated for thermophilic enzymes. The enzyme represents one of the most thermostable xylanases ever reported with biotechnological potential. KEY POINTS: • Hyperthemophilic xylanase X11PNQ was obtained by rational design engineering. • X11PNQ showed specificity to prebiotic xylooligosaccharides (XOS) at 85 °C with improved t1/2 at 90 °C. • Novel thermostabilization by π-amide interaction was demonstrated by MD/QM.

Keywords: Hyperthermophilicity; Molecular dynamic simulation; Oligosaccharides; Rational design; Xylanase.

MeSH terms

  • Cellulose / metabolism
  • Disaccharides / chemistry
  • Disaccharides / metabolism
  • Endo-1,4-beta Xylanases* / chemistry
  • Endo-1,4-beta Xylanases* / genetics
  • Endo-1,4-beta Xylanases* / metabolism
  • Enzyme Stability*
  • Glucuronates* / chemistry
  • Glucuronates* / metabolism
  • Hot Temperature
  • Hydrogen Bonding
  • Metagenome
  • Molecular Dynamics Simulation*
  • Oligosaccharides* / chemistry
  • Oligosaccharides* / metabolism
  • Quantum Theory
  • Substrate Specificity
  • Xylans* / chemistry
  • Xylans* / metabolism

Substances

  • Endo-1,4-beta Xylanases
  • Xylans
  • Oligosaccharides
  • Glucuronates
  • xylooligosaccharide
  • bagasse
  • Cellulose
  • Disaccharides
  • xylobiose