A quantitative indicator diagram for lytic polysaccharide monooxygenases reveals the role of aromatic surface residues in HjLPMO9A regioselectivity

PLoS One. 2017 May 31;12(5):e0178446. doi: 10.1371/journal.pone.0178446. eCollection 2017.

Abstract

Lytic polysaccharide monooxygenases (LPMOs) have changed our understanding of lignocellulosic degradation dramatically over the last years. These metalloproteins catalyze oxidative cleavage of recalcitrant polysaccharides and can act on the C1 and/or C4 position of glycosidic bonds. Structural data have led to several hypotheses, but we are still a long way from reaching complete understanding of the factors that determine their divergent regioselectivity. Site-directed mutagenesis enables the investigation of structure-function relationship in enzymes and will be of major importance in unraveling this intriguing matter. In this context, it is crucial to have an enzyme assay or screening approach with a direct correlation with the desired functionality. LPMOs render this search extra challenging due to their insoluble substrates, complex pattern of reaction products and lack of synthetic standards of most oxidized products. Here, we describe a regioselectivity indicator diagram based on the time-course of only 2 HPAEC-PAD signals. The diagram was successfully used to confirm the hypothesis that aromatic surface residues influence the C1/C4 oxidation ratio in Hypocrea jecorina LPMO9A. Consequently, the diagram should become a valuable tool in the search towards better understanding and engineering of regioselectivity in LPMOs.

MeSH terms

  • Chromatography, Ion Exchange
  • Genetic Vectors
  • Mixed Function Oxygenases / chemistry
  • Mixed Function Oxygenases / genetics
  • Mixed Function Oxygenases / isolation & purification
  • Mixed Function Oxygenases / metabolism*
  • Mutagenesis, Site-Directed
  • Pichia / genetics
  • Polysaccharides / metabolism*

Substances

  • Polysaccharides
  • Mixed Function Oxygenases

Grants and funding

The company Bio-Prodict BV provided support in the form of salaries for author HJ, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.