Phylogenetic study of polyketide synthases and nonribosomal peptide synthetases involved in the biosynthesis of mycotoxins

• Published in: Toxins Vol. 5; no. 4; pp. 717 - 742
• Main Authors: Gallo, Antonia, Ferrara, Massimo, Perrone, Giancarlo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.04.2013; MDPI
• Subjects: acyl-transferase; adenylation; Amino Acid Sequence; condensation; Databases, Protein; Fungal Proteins - chemistry; Fungal Proteins - genetics; Fungal Proteins - metabolism; Fungi - enzymology; Fungi - genetics; Genes, Fungal; Mycotoxins - biosynthesis; non-ribosomal peptide synthetase; Ochratoxins - biosynthesis; Peptide Synthases - chemistry; Peptide Synthases - genetics; Peptide Synthases - metabolism; phylogenies; Phylogeny; polyketide synthase; Polyketide Synthases - chemistry; Polyketide Synthases - genetics; Polyketide Synthases - metabolism; Protein Structure, Tertiary; secondary metabolites; Sequence Alignment; β-ketosynthase
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins5040717

Polyketide synthase (PKSs) and nonribosomal peptide synthetase (NRPSs) are large multimodular enzymes involved in biosynthesis of polyketide and peptide toxins produced by fungi. Furthermore, hybrid enzymes, in which a reducing PKS region is fused to a single NRPS module, are also responsible of the synthesis of peptide-polyketide metabolites in fungi. The genes encoding for PKSs and NRPSs have been exposed to complex evolutionary mechanisms, which have determined the great number and diversity of metabolites. In this study, we considered the most important polyketide and peptide mycotoxins and, for the first time, a phylogenetic analysis of both PKSs and NRPSs involved in their biosynthesis was assessed using two domains for each enzyme: β-ketosynthase (KS) and acyl-transferase (AT) for PKSs; adenylation (A) and condensation (C) for NRPSs. The analysis of both KS and AT domains confirmed the differentiation of the three classes of highly, partially and non-reducing PKSs. Hybrid PKS-NRPSs involved in mycotoxins biosynthesis grouped together in the phylogenetic trees of all the domains analyzed. For most mycotoxins, the corresponding biosynthetic enzymes from distinct fungal species grouped together, except for PKS and NRPS involved in ochratoxin A biosynthesis, for which an unlike process of evolution could be hypothesized in different species.