## 5 AMGs with the Potential to Impact Regulatory Factors  
Among the 153 sequenced cyanophage genomes, 65 cyanophages possess putative sigma factors (RpoD/RpoS) (Figure 2). The cyanophage putative sigma factors have high amino acid sequence homology with \(\sigma\)70-type sigma factors in cyanobacteria [97]. As a transcription initiator, the sigma factor binds to the specific sequence and regulates gene transcription. The metabolism, growth, and phenotype of bacteria are affected by the expression of sigma factors. In _Escherichia coli_, there are several sigma factors, including \(\sigma\)70 (RpoD), which is responsible for exponential growth, \(\sigma\)38 (RpoS), which is a stationary phase sigma factor, and the flagellar sigma factor \(\sigma\)28 (RpsD) [98; 99]. Cyanobacteria also possess sigma factors in the \(\sigma\)70 family, of which there are three groups categorized upon their amino acid sequences, including sigma factors that control the expression of essential cell growth genes [100], sigma factors that are not essential for cell survival, and other \(\sigma\)70 factors. Furthermore, there are several other putative sigma factors such as \(\sigma\)38 in cyanophage genome sequences. In a recent study, the carbon metabolism in _Synechococcus elongatus_ PCC 7942 was modified through the expression of putative sigma factors from _Synechococcus_ phages. After the expression of putative RpoD from phage S-CBS2 and putative RpsD4 from phage S-CBS3, the growth of _S. elongatus_ PCC 7942 was enhanced noticeably. Through metabolome analysis, the acetyl-CoA concentration was found to increase 3.2-fold and 1.9-fold following expression of the putative RpoD from S-CBS2 and the putative RpsD4 from S-CBS3, respectively [97]. It is possible that the host carbon metabolism can be affected by sigma factors encoded by the cyanophages after infection. Some genes involved in cofactor B12 synthesis have also been discovered in the sequenced cyanophage genomes including the genes _cobA_ (38/153), _cobO_ (37/153), and _cobS_ (52/153). As an ancient enzyme, ribonucleotide reductase (RNR) reduces ribonucleotides to deoxyribonucleotides before DNA synthesis. Depending on their interaction mechanism with oxygen and the different ways for the generation of thiol radicals, RNRs can be grouped into three classes through their reactivity with O\({}_{2}\)[101]. Class I RNRs are O\({}_{2}\)-dependent; class IIRNRs are O\({}_{2}\)-independent; and class III RNRs are O\({}_{2}\)-sensitive. Adenosylcobalamin (cofactor B12) is a key cofactor of class II RNRs that are commonly observed in cyanophages and cyanobacteria. Genes _cobA_, _cobO_, and _cobS_, which were found in the sequenced cyanophage genomes, also play a key role in the adenosylcobalamin (cofactor B12) biosynthesis pathway (Scheme 2C) [102]. The gene _mazG_ encoding dNTP pyrophosphatase activity, MazG, was found in 64 of the 153 sequenced cyanophage genomes (Figure 2). In _E. coli_, MazG acts on the signaling nucleotide guanosine tetraphosphate (ppGpp) with one-third of the _E. coli_ genome being regulated by MazG [103]. As a regulator, MazG responds to nutrient stress and programmed cell death [104; 105]. In cyanophages, as a global transcriptional regulator through the modulation of ppGpp levels, MazG regulates many metabolic pathways and may also extend the cell survival period under phage infection stress [106]. However, MazG has high non-canonical NTP specificity, indicating the need for the identification of the substrate for each MazG by solving crystal structures and activity analysis [107]. The exact function and substrate of cyanophage MazG would, therefore, need to be cautiously interpreted [21]. As a translational repressor, the RegA protein regulates the expression of several phage early mRNAs in the bacteriophage T4 [108]. In the sequenced cyanophage genomes, 48/153 RegA proteins were observed. In the process of bacteriophage T4 infection, DNA polymerase accessory proteins and membrane proteins of undefined functions are regulated by RegA.