Laccase (EC 1.10.3.2) is a copper-containing polyphenol oxidase that belongs to the blue copper oxidase (MCO) family [1,2]. It was first discovered in the Japanese lacquer tree Rhus Vernicifera [3,4]. Subsequently, laccases were found in different plant species [5], microbes [6,7], and animals [8]. There have been more investigations on microbial laccases than on animal and plant laccases, for which there have been relatively few. Microbial laccases are divided into fungal laccases and bacterial laccases. Bacterial laccase mainly plays a role in melanin production, spore wall defense, morphological change, and copper ion detoxification [9,10]. Fungal laccase is mainly related to pigment generation, plant disease, and lignin degradation [11,12]. Plant laccase is closely related to lignin biosynthesis [13]. At the same time, the primary function of animal laccase protein is to control the ossification of the epidermis [14].

Laccase is a glycoprotein with a molecular mass ranging from 50 to 140 kDa. Their amino acid sequence can span from 220 to 800 amino acids and may contain three cupredoxin-like domains. These domains bind copper centers involved in intermolecular electron transfer reactions and constitute the catalytic core of laccases (Figure 1) [15]. The active copper center of laccase generally contains four copper ions: a type I copper ion (T1-Cu), a type II copper ion (T2-Cu), and two type III copper ions (T3-Cu). T1-Cu is a mononuclear center that can gain electrons from the substrate and then transfer them to the trinuclear cluster (TNC), and the oxidation of the substrate occurs there. T2-Cu is a single-electron acceptor, whereas T3-Cu forms coupled ion pairs and is a double-electron acceptor. T2-Cu and T3-Cu together form a trinuclear cluster (TNC). Oxygen accepts four electrons and four protons to form water, which joins the bulk solvent [16,17]. Laccases can perform the single-electron oxidation of the substrate without using hydrogen peroxide while reducing molecular oxygen to water; therefore, they have a surprisingly broad substrate spectrum and can oxidize simple diphenols, polyphenols, diamines, and aromatic amines. The optimum temperature and pH of laccases depend on the enzyme source and substrate properties; those ranges are, respectively, from 20 °C to 75 °C and 3 to 8 (Table 1).

As an oxidase, the ability of laccase to oxidize the substrate is directly related to its redox potential (E0) [33,34]. E0 is an important characteristic of the catalytic oxidation capacity of laccase, which is the energy required for laccase to capture an electron from a reducing substrate. The E0 is critical to the reactivity of laccase and the overall reaction characteristics. Laccase can directly oxidize substrates with low E0, whereas some mediators are needed to assist laccase in oxidizing substrates with high E0. Adding a mediator not only effectively improves the reaction efficiency of laccase but also expands the scope of the substrate. For instance, with the mediator’s help, laccase can oxidize nonphenolic structures with high E0 and is used in pulp bleaching [35]. Recently, laccase and the laccase–mediator system (LMS) have received extensive attention in green catalysis, such as synthesizing complex organic compounds, the selective modification of natural products, and the degradation of harmful substances [36,37,38,39]. For example, the C–N bond breakage of amines catalyzed by laccase is essential for synthesizing amino acids and nucleosides [40,41]. Existing research indicates that using Pleurotus ostreatus laccase and its natural mediator (syringaldehyde) to catalyze C–C bond breakage results in the removal of up to 100% and 85% of BPA at concentrations of 0.44 and 0.88 mmol/L in wastewater within 1 h [42].

2. The Effect of the Mediator System on Laccase Catalysis