DyP-Type Peroxidases: Recent Advances and Perspectives

Abstract

In this review, we chart the major milestones in the research progress on the DyP-type peroxidase family over the past decade. Though mainly distributed among bacteria and fungi, this family actually exhibits more widespread diversity. Advanced tertiary structural analyses have revealed common and different features among members of this family. Notably, the catalytic cycle for the peroxidase activity of DyP-type peroxidases appears to be different from that of other ubiquitous heme peroxidases. DyP-type peroxidases have also been reported to possess activities in addition to peroxidase function, including hydrolase or oxidase activity. They also show various cellular distributions, functioning not only inside cells but also outside of cells. Some are also cargo proteins of encapsulin. Unique, noteworthy functions include a key role in life-cycle switching in Streptomyces and the operation of an iron transport system in Staphylococcus aureus, Bacillus subtilis and Escherichia coli. We also present several probable physiological roles of DyP-type peroxidases that reflect the widespread distribution and function of these enzymes. Lignin degradation is the most common function attributed to DyP-type peroxidases, but their activity is not high compared with that of standard lignin-degrading enzymes. From an environmental standpoint, degradation of natural antifungal anthraquinone compounds is a specific focus of DyP-type peroxidase research. Considered in its totality, the DyP-type peroxidase family offers a rich source of diverse and attractive materials for research scientists.

Keywords: DyP; DyP-type peroxidase; antifungal anthraquinone compounds; cargo protein; encapsulin; hydrolase; iron uptake; life cycle; lignin degradation; nano compartment; oxidase; structure-based sequence alignments.

Figure 1

DyP phylogenetic tree. The tree was constructed with the maximum-likelihood method using RAxML-NG [61] with multiple sequence alignments of DyP amino acid sequences generated by the MAFFT [62] program. Percentages of bootstrap values obtained from 1000 bootstrap replicates are shown at the nodes. The best-fit model of evolution of the alignment was determined using ModelTest-NG [63]. Branches and labels of different phyla are shown in different colors: green, actinobacteria; blue, firmicutes; red, proteobacteria; purple, cyanobacteria; orange, basidiomycota. Reference numbers for each DyP are shown in parentheses. Structures of representative DyPs of the three classes are shown on the right: Class I, DtPA (PDB ID: 6gzw); Class P, DtPB (PDB ID: 6yrj); Class V: DyP (PDB ID: 3afv).

Figure 2

Catalytic cycle of a typical heme peroxidase. Oval denotes the heme plane in the enzyme. AH is a substrate.

Figure 3

Schematic diagram of two-electron oxidation of substrates by a DyP-type peroxidase, proposed in [20]. Left, compound I; center, ES complex; right, resting state. Oval denotes the heme plane in the enzyme. Asp is the catalytic residue. S and P denote substrate and product, respectively. In a general peroxidase, compound I changes to compound II with one electron reduction, as shown in Figure 2, but in this scheme, compound I of DyP-type peroxidases changes to the resting state directly through two-electron reduction.

Figure 4

Comparison of proposed anthraquinone degradation mechanisms. A, H₂O from Wet compound I attacks the anthraquinone frame, causing enzymatic hydrolysis [44]. Oval denotes the heme plane in the enzyme. B, Spontaneous hydrolysis generates phthalic acid, but predicted intermediates have not been detected [66].

Figure 5

Schematic depiction of efeUOB and fepABC operons. Both operons are regulated by the Fur repressor (blue oval). efeB and fepB are orthologs of each other and encode DyP-type peroxidases.