# Isolation and Characterization of a Novel Cyanophage Encoding Multiple Auxiliary Metabolic Genes
## 3 Results and Discussion
### AMGs Encoded by S-SZBM1 Re-Program Phase-Host Interactions
As has been found in many other cyanophages, cyanophage S-SZBM1 contains a set of photosynthetic related genes potentially functioning in the alteration of host metabolic process during infection. Figure 4: Representative AMGs in cyanophage S-SZBM1 and its most related 32 cyanophages. AMGs within different functional categories are indicated by color noted above. In addition to photosystems, cyanophages also influence phototrophic energy by regulating _zwf_, _gnd_, and _talc_ genes encoding pentose phosphate pathways (PPP) enzymes, as well as _cp12_, a gene encoding an allosteric repressor of two Calvin cycle enzymes [48; 49]. Cyanophage S-SZBM1 was found to carry both _cp12_ and _talc_. The gene _cp12_ directs carbon flux from the Calvin cycle to the PPP, while _talc_ encodes a transalodalose. The synergetic expression of _cp12_ and _talc_ has been reported to increase the host NADPH/NADP ratio upon infection, while phage-augmented NADPH production subsequently fuels deoxynucleotide biosynthesis for phage replication [17]. Cyanophage S-SZBM1 carries a carbamoyltransferase homology, which can catalyze the first step of de novo pyrimidine biosynthesis and subsequently increase nucleotide synthesis during infection and, therefore, facilitate the viral genome replication [62]. In addition to benefiting phage nucleotide synthesis, some cyanophage-encoded genes, such as cell protection genes, can control host environment-sensing regulatory proteins to ensure viral replication under unfavorable conditions. A small heat shock protein, which is characterized by an \(\alpha\)-crystalline domain surrounded by highly variable N-terminal and C-terminal regions and plays a role in proteostasis at high temperature, is also present in the genome of cyanophage S-SZBM1 [63]. As well, a gene _prnA_ carried by cyanophage S-SZBM1, which can catalyze the first step in the biosynthesis of pyrrolnirn, was speculated to provide antibiotic protection to its host [14; 64; 65; 66]. Moreover, cyanophage S-SZBM1 also possesses _prdx_ and _nrdC_ genes, which might be involved in cell protection. For instance, they were suggested to enhance the defense against potential oxidative damage and manipulate stress responses in host cells via changes in redox state, respectively [67; 68]. Cyanophage S-SZBM1 possesses a gene, _phoH_, which has the highest frequency of occurrence in sequenced phage genomes among pho regulon [69]. As we know, the gene _pstS_ has been proven to encode a phosphate-binding protein involved in phosphate transport, while _phoA_ presumably catalyzes the removal of phosphate groups from a variety of substrates to free bound phosphates for viral use [68; 70]. Similar to _pstS_ and _phoA_, _phoH_ has always been speculated to play a crucial role in assisting phage genome replication under phosphorus-depleted conditions [16; 69]. However, no evidence has been provided for _phoH_ to be related to phosphate stress, and the role of _phoH_ in infected cells is still unclear. The gene _mazG_ encodes pyrophosphohydrolase, which is universally distributed in cyano-myoviruses [42; 44; 58]. Previous studies showed that the _mazG_ gene in cyanophages is not clustered with the host _mazG_ gene, suggesting cyanophage-encoded _mazG_ might arise outside cyanobacteria [44; 71]. Recent investigation has demonstrated that neither the _Synechococcus_ nor cyanophage _mazG_ demonstrated detectable hydrolytic activity towards (p)ppGpp [72]. Instead, the cyanophage _mazG_ preferentially hydrolyze dGTP and dCTP deoxyribonucleotides from the host genomes, allowing it to reuse building blocks from its host to replicate the cyanophage genome [72]. Multiple copies of 2 OG-Fe(II) oxygenase are widely present in cyanophage S-SZBM1 (nine copies) as well as other cyano-myoviruses, while all of these 2 OG-Fe(II) oxygenase are conserved in cyanophage S-SZBM1 genome.