AptE belongs to a biosynthetic cluster named hphABCD. Genes from hph cluster are often detected in the very same genomic area as apt and spu clusters, which both solutions, HSPA5 list Anabaenopeptins and Spumigins, are peptides displaying protease inhibitory activity and CCR3 Formulation homoamino acids. A genomic evaluation of Sphaerospermopsis torques-reginae ITEP-024 demonstrated that each Spumigin and Anabaenopeptin clusters have been present in proximity inside the genome. In amongst each clusters,Toxins 2021, 13,24 ofthe hphABCD biosynthetic cluster and extra genes were detected within this region, which a comparable organization was also visualized in Nodularia spumigena CCY9414 [107]. The hph genes are accountable for the biosynthesis of Hph and Hty, nonproteinogenic amino acids generally identified in both anabaenopeptin and spumigin [116]. Therefore, indicating that HphA will not be accountable for ureido linkage formation but behind the provide of both Hph and Hty. Also, the presence with the homophenylalanine and homotyrosine biosynthetic enzymes in this area could suggest that this cluster is supplying both homoamino acids for APs and Spumigins [107]. In accordance with Lima and co-workers [107], Shishido and colleagues [56] also visualized that from 56 genomes analyzed containing the apt cluster all demonstrated to possess the hph biosynthetic cluster, except for Scytonema hofmanii PCC 7110 and Candidatus Entotheonella sp. TSY. The genes encoding the proteins HphABCD were often discovered upstream or downstream with the AP cluster, supporting the hypothesis about their roles in providing homoamino acids to APs [107]. Thus, homoamino acids are created by the HphABCD enzymes after which incorporated by the NRPS apparatus. Furthermore, these non-proteinogenic amino acids also can be further modified by the NRPS enzymes, taking into consideration that residues at position 5 are mainly methylated by the N-methylation domain in the second module of AptC. However, methylation of residues at position four was also visualized, such in Ferintoic acids A and B [39], Anabaenopeptin E [37], 863, 891, 848, and 882 [24]. The final step for Anabaenopeptin production is mediated by a Te-domain, which can be usually linked together with the termination approach on the biosynthesis of NRPS peptides. Hence, following the incorporation on the last residue, one example is, L-Phenylalanine in AP B (Figure 11), these domains is usually involved together with the release with the peptide by hydrolysis, or even cyclization involving peptidic or ester bonds [19,106]. The final NRPS enzymes AptD and its homologs [18,111] bear the thioesterase domain, suggesting then their function as the termination step. Apart from these typical alterations for the amino acid residues discussed, various variants of APs have been discovered with unique modifications, which include ethylated (Figure two, Figure 3, and Figure five), acetylated, and oxidized residues [22,24,34]. Along with such modifications throughout the elongation methods by the NRPS, an evaluation of cytochrome P450 monooxygenases from cyanobacteria revealed that some proteins of this class may perhaps be associated to anabaenopeptin modifications. In Synechococcus sp. PCC 7502, it had been recommended that a P450 belonging to CYP110 is involved in the production of Anabaenopeptin NZ857. Anabaena sp. TAU NZ-3-1 was capable to coproduce this anabaenopeptin and APs NZ 825 and NZ841. Anabaenopeptin NZ857 differs from AP NZ825 and AP NZ841 by the amount of oxidized residues at positions four and six. Anabaenopeptin NZ857 has in both positions 4 an