Biological and Medicinal Chemistry

Discovery and molecular elucidation of pervasive Aflatoxin B1 oxidation activity in the laccase superfamily

Authors

  • Ryan Caster University of California, Davis, Genome Center ,
  • Emma Luu University of California, Davis, Department of Biophysics ,
  • Ka Yi Tsui University of California, Davis ,
  • Jun Yang University of California, Davis, Department of Entomology and Nematology ,
  • Augustine Arredondo University of California, Davis, Department of Chemistry ,
  • Youtian Cui University of California, Davis, Genome Center ,
  • Hannah Shafaat The Ohio State University, Department of Chemistry and Biochemistry ,
  • Guangtao Zhang Mars Incorporated, Global Food Safety Center ,
  • Bruce Hammock University of California, Davis, Department of Biochemistry, Molecular, Cellular and Developmental Biology & University of California, Davis, Department of Pharmacology and Toxicology, Agricultural and Environmental Chemistry ,
  • Dean Tantillo University of California, Davis, Department of Chemistry ,
  • Justin Siegel University of California, Davis, Department of Biochemistry and Molecular Medicine & University of California, Davis, Department of Chemistry

Abstract

Aflatoxins are mutagenic mycotoxins which are believed to impact over a billion people every year, particularly in the developing world, and, when consumed, lead to stunting, immunosuppression, and liver cancer. With the worsening of climate change, molds and their toxic secondary metabolites will become an even greater risk to humanity. In this work we use in vitro and in silico methodologies to evaluate the potential for and propose the use of multicopper oxidases, specifically laccases, to enzymatically degrade aflatoxin B1 (AFB1), a highly mutagenic mycotoxin, to a safer byproduct. A panel of assays was performed on 45 members of the multicopper oxidase family with 20 different enzymes showing the ability to degrade AFB1 and establishing the pervasiveness of this activity in the family. In order to better understand how laccases oxidize AFB1, we utilized density functional theory to identify likely atoms within AFB1 for oxidation to occur. Once a reaction scheme had been established, we employed computational docking with Rosetta to ascertain which structural features are likely to contribute to AFB1 binding. These predictions can provide insight for future efforts to optimize enzymes for detoxifying AFB1.

Content

Thumbnail image of Manuscript_w_Authors.pdf

Supplementary material

Thumbnail image of Supporting_Information_w_Authors.pdf
Supplementary Supporting Material
These figures provide additional data and visualizations that support the main manuscript text.

Supplementary weblinks

RosettaLigand Modeling Protocol
A Github repository containing the RosettaLigand modeling protocol used for docking simulations