methyltransferase domain (AnaC), which may be associated with typical functions encountered in APs, for instance D-Lys and N-methylated amino acids, respectively. Only one cluster was detected within this organism, and it was attributed for the biosynthesis of all four peptides produced: Anabaenopeptin A, B, F, and Oscillamide Y, which differ by the combinatory of two residues in two distinct positions: (Tyr/Arg)-Lys-(Val/Ile)-Hty-MeAla-Phe. Therefore, this phenomenon indicates that these NRPSs demonstrated a particular degree of promiscuity with regards to their substrates and A-domains, as diverse amino acids can interact together with the very same catalytic web-site [18]. Rouhiainen and co-workers [110] detected gene clusters related to the production of APs in Anabaena sp. 90, Nodularia spumigena CCY9414, and Nostoc punctiforme PCC3102. In Anabaena sp. 90, 5 Open Reading Frame (ORF) have been identified to become encoding NRPSs (aptA1, aptA2, aptB, aptC, and aptD) and two extra genes to be encoding proteins with similarity to HMGL-family (aptE) and ABC-transporter protein (aptF). When in comparison with the clusters identified in N. spumigena and N. punctiforme, 4 NRPS and two homolog proteins to AptE and -F had been also detected, indicating that Anabaena sp. had an extra NRPS gene (aptA1 and aptA2). Similar to AnaA from Planktothrix rubescens NIVA-CYA 98, AptA1 and AptA2 also have an epimerase domain indicating their function asToxins 2021, 13,20 ofinitial enzymes, and AptC possessing the N-methyltransferase domain as AnaC [110]. The proteins AptA1/AptA2, AptB, AptC, and AptD are homologs for the NRPS proteins AnaA, AnaB, AnaC, and AnaD, sharing the same functions, respectively. A genomic analysis of Sphaerospermopsis torques-reginae ITEP-024 accomplished by Lima and colleagues [107] demonstrated that the apt gene cluster is close towards the spumigin cluster. Each AP and spumigin are peptides with protease inhibitory activity which commonly possess Homophenylalanine and Homotyrosine residues, then indicating that both NRPS apparatus share a biosynthetic cluster related to the production of these nonproteinogenic residues. The apt gene cluster of S. torques-reginae strain features a equivalent organization for the anabaenopeptin clusters from Anabaena, Nodularia, Nostoc, and Plaktothrix [18,110]. Therefore, its cluster also holds four genes encoding a six-module NRPS (aptABCD), where the Te-domain is present at the last module, then being accountable for the final step of AP production, similarly to other NRPS solutions [107]. Entfellner and co-workers [57] suggested that the AP cluster may be transferred amongst cyanobacterial species as a consequence of horizontal gene transfer (HGT). This hypothesis is supported by the high similarity BRD2 Formulation visualized in between the apnA-E cluster from Planktothrix and Microcystis composed by apnA, apnB, apnC, apnD and apnE, which genes codified proteins homologs to AnaA/AptA, AnaB/AptB, AnaC/AptC, AnaD/AptD, and AnaE/AptF, respectively. Some strains belonging to the Planktothrix genus demonstrated to possess the same AP cluster, but not all of them, hence suggesting that the popular ancestors of those organisms did not have the NRPS apparatus for AP biosynthesis, which could be visualized by a phylogenetic evaluation using apnA-E clusters as CDK16 Purity & Documentation biological markers. By phylogenetic analysis of distinct sequences of anabaenopeptin cluster, it might be inferred that an ancestral cluster was introduced into the chromosome of a Planktothrix strain and diversified into various variants, which could