Enzymes for Detoxification of Various Mycotoxins: Origins and Mechanisms of Catalytic Action

Abstract

Mycotoxins are highly dangerous natural compounds produced by various fungi. Enzymatic transformation seems to be the most promising method for detoxification of mycotoxins. This review summarizes current information on enzymes of different classes to convert various mycotoxins. An in-depth analysis of 11 key enzyme mechanisms towards dozens of major mycotoxins was realized. Additionally, molecular docking of mycotoxins to enzymes' active centers was carried out to clarify some of these catalytic mechanisms. Analyzing protein homologues from various organisms (plants, animals, fungi, and bacteria), the prevalence and availability of natural sources of active biocatalysts with a high practical potential is discussed. The importance of multifunctional enzyme combinations for detoxification of mycotoxins is posed.

Keywords: antidote; biochemical mechanism; conversion; detoxification; enzyme; molecular modeling; mycotoxin; origins.

Figure 1

Chemical structures of some mycotoxins.

Figure 2

(A) Structure of aflatoxin dialdehyde reductase AKR7A1 (PDB 1gve) containing aflatoxin B₁ in its active center, and (B) scheme of substrate conversion with AKR7A1. Position and geometry of substrate binding was determined using molecular docking with Autodock Vina as described [15] (see Appendix A for details). Molecular surface of substrate was calculated using Gamess-US as described [16] and is shown as mesh. Within reaction scheme, OH-groups marked with blue are introduced by cytochromes, and oxygens marked with red are modified by AKR7A1. (C) Phylogenetic tree of organisms possessing homologous enzymes found with BLAST.

Figure 3

(A) Structure of cytochrome P450 (PDB 4i8v) containing sterigmatocystin in its active center, and (B) scheme of substrate conversion with cytochrome. Position and geometry of substrate binding was determined as described early. (C) Phylogenetic tree of organisms possessing homologous enzymes found with BLAST.

Figure 4

(A) Structure of gliotoxin oxidoreductase GliT (PDB 4ntc) containing gliotoxin in its active center, and (B) scheme of substrate conversion with GliT. Position and geometry of substrate binding was determined as described early. (C) Phylogenetic tree of microorganisms possessing homologous enzymes found with BLAST.

Figure 5

(A) Structure of zearalenone hydrolase ZHD (PDB 3wzl) containing zearalenone in its active center, and (B) scheme of substrate conversion with ZHD. Position and geometry of substrate binding was determined as described early. (C) Phylogenetic tree of microorganisms possessing homologous enzymes found with BLAST.

Figure 6

(A) Structure of ochratoxinase OTase (PDB 4c5y) containing ochratoxin A in its active center, and (B) scheme of substrate conversion with OTase. Position and geometry of substrate binding was determined as described early. (C) Phylogenetic tree of microorganisms possessing homologous enzymes found with BLAST.

Figure 7

(A) Structure of enzyme PGUG containing patulin in its active center, and (B) scheme of substrate conversion with PGUG. Amino acid sequence was obtained from GenBank EDK41095.2 and folded using I-TASSER server. Position and geometry of substrate binding was determined as described early. (C) Phylogenetic tree of microorganisms possessing homologous enzymes found with BLAST.

Figure 8

(A) Structure of organophosphorus hydrolase (PDB 1qw7) containing patulin in its active center, and (B) scheme of substrate conversion with organophosphorus hydrolase. Position and geometry of substrate binding was determined as described early. (C) Phylogenetic tree of microorganisms possessing homologous enzymes found with BLAST.

Figure 9

(A) Structure of enzyme FUMD containing fumonisin B₁ in its active center, and (B) scheme of substrate conversion with FUMD. Amino acid sequence was obtained from UniProt D2D3B6 and folded as described early. Position and geometry of substrate binding was determined as described early. (C) Phylogenetic tree of microorganisms possessing homologous enzymes found with BLAST.

Figure 10

(A) Structure of enzyme ErgA containing ergotamine in its active center, and (B) scheme of substrate conversion with ErgA. Amino acid sequence was obtained from [132] and folded as described early. Position and geometry of substrate binding was determined as described early. (C) Phylogenetic tree of microorganisms possessing homologous enzymes found with BLAST.

Figure 11

(A) Structure of glycosyltransferase OsUGT79 (PDB 5tmd) containing deoxynivalenol in its active center, and (B) scheme of substrate conversion with OsUGT79. Position and geometry of substrate binding was determined as described early. (C) Phylogenetic tree of microorganisms possessing homologous enzymes found with BLAST.

Figure 12

(A) Structure of 3-acetyltransferase TRI101 (PDB 2rkv) containing T-2 toxin in its active center, and (B) scheme of substrate conversion with TRI101. Position and geometry of substrate binding was determined as described early. (C) Phylogenetic tree of microorganisms possessing homologous enzymes found with BLAST.