# Fungal Pigments and Their Roles Associated with Human Health
## 3 Biosynthesis of Fungal Pigments
### Shikimate Pathways  
Aromatic amino acids act as the precursor of various fungal secondary metabolites such as pigments and vitamins [95]. In the fungal phylum _Basidiomycota_, tyrosine is the precursor of a distinct class of pigments, the betalains, solely present in the genera of _Amanita_ and _Hygracybe_[96; 97]. In the phylum _Ascomycota_, tyrosine-derived pigments, such as melanin and tyrosine betaine, are thought to contribute to stress tolerance (e.g., temperature, radiation) [98; 99] and pathogenicity [100; 101].  
The shikimate pathway is present in the prokaryotes, microbial eukaryotes and plants studied. However, it is absent in those animal species investigated [102]. This pathway links carbohydrate metabolism to the biosynthesis of aromatic compounds. Metabolically, the shikimate pathway is a seven-step route utilized by fungi for the biosynthesis of aromatic amino acids like phenylalanine (Phe), tyrosine (Tyr), and tryptophan (Trp), as well as para-aminobenzic acid, via the central intermediates shikimic and chorismic acids [86]. The first step involves the condensation of the glycolytic intermediate phosphoenol pyruvate and pentose phosphate pathway intermediate erythrose-4-phosphate to yield a seven-carbon heterocyclic compound, 3-deoxy-D-arabinose-heptulosonate-7-phosphate derivative (DAHP). The second step involves the generation of a highly substituted cyclohexane derivative, 3-dehydroquinate, by the replacement of the exocyclic C\({}_{7}\) of DAHP by the ring oxygen. The remaining five steps involve the introduction of a side chain and two of the three double bonds that convert this cyclohexane into a benzene ring, the core of aromatic amino acids [5]. The metabolic routes may vary for different classes of pigments.  
The pigments produced via the shikimate pathway are generally water-soluble phenolic compounds, including terpenly and pulvinic acids. Studies of \(p\)-terphenyl as a family of the mushroom pigments were initiated in 1877. Isolation of polyporic acid, atromentin and thelephoric acid represented the inception of the chemical investigation of fungal pigments. The elucidation of the structures of polyporic acid and atromentin by [PERSON] is recognized as a milestone in organic chemistry [103]. It has been demonstrated that some terphenyls display biological activities, such as immunosuppressive, antithrombotic, anticoagulant, neuroprotective, 5-lipoxygenase inhibitory (for the treatment of inflammatory bowel disease), and cytotoxic activities [104].  
Many fungi have evolved pathways utilizing the aromatic products of shikimate metabolism (Figure 7). The initial steps in the biogenesis of _p_-terphenyls are the well-known reactions of primary metabolism flowing from shikimate to chorismic acids and subsequently to arylpyruvate acids. Experiments involving the feeding of \({}^{13}\)C- and \({}^{14}\)C-labeled precursors to fungal cultures revealed that _p_-terphenyls are assembled by initial condensation between two molecules of unbranched phenylpropanolic precursors, either phenylpyruvate acid or phenylalanine. Previous studies also revealed the involvement of 4-hydroxyphenylpyruvate acids or tyrosine in the initial condensation during the biosynthesis of terphenylquinones such as atromentin [105]. Atromentin is known as a key intermediate for further conversions, for instance, to more highly hydroxylated terphenylquinones and pulvinic acids [106; 107].  
Figure 7: Shikimate pathway leading to biosynthesis of _p_-terphenyls.