## 4 AMGs with the Potential to Impact Central Carbon Metabolism  
In cyanobacteria, energy (ATP) and reducing power (NADPH) produced by ATP synthase and ferredoxin NADP\({}^{+}\) reductase (FNR) during photosynthesis are mostly used for carbon fixation in the Calvin cycle [80]. However, cyanophage infection can drastically alter the energy flow. This research reveals that more than 20% of cyanophage genomes contain a _cp12_ gene, which encodes for a Calvin cycle inhibitor. In cyanobacteria, the Calvin cycle is a key pathway for carbon fixation. Two essential enzymes of the Calvin cycle are phosphoribulokinase (PRK) and glyceraldehyde-3-phosphate dehydrogenase (GADPH/Gap2). The first step of the cycle, PRK, catalyzes the conversion of D-ribulose 5-phosphate (Ru5P) to D-ribulose 1,5-biphosphate (RuBP), consuming ATP [81]. GADPH catalyzes the conversion of D-glycerate 1,3-biphosphate (BPG) to the end product glyceraldehyde 3-phosphate (GAP), consuming NADPH (Scheme 2A). The Calvin cycle inhibitor CP12 can inhibit the function of these two enzymes by redirecting the carbon flux from GAP synthesis to the pentose phosphate pathway (PPP) and can reduce the consumption of ATP and NADPH. In a study of CP12, particularly in the light and dark cycle of _Prochlorococcus_, researchers found that the _cp12_ gene was maximally expressed at night, and in that in dark cycle, carbon flux was directed from the Calvin cycle to PPP in _Prochlorococcus_[82]. In addition to the Calvin cycle, PPP also plays a key role in central carbon metabolism in cyanobacteria [63]. Three PPP enzymes were found in the sequenced cyanophage genomes, i.e., transaldolase (_talc_, 96/153), glucose-6-phosphate dehydrogenase (_zwf_, 25/153), and 6-phosphogluconate dehydrogenase (_gnd_, 22/153) (Scheme 2A). The sequence of TaIC is substantially different from that of its host homolog TalB. Through multiple sequence alignment analysis, when compared with TalB, TalC contained numerous deletions; however, there were no changes in the active site residues that were important for catalysis [83; 84]. Through activity analysis, the product of the genes _talC_ and _talB_ could catalyze the conversion of sedoheptulose 7-phosphate (S7P) and GAP to erythrose 4-phosphate (E4P) and fructose 6-phosphate (F6P) (Scheme 2A) [63]. Based on a comparison of the kinetic properties of TaICs with TalBs, the phage transaldolase may have more advantages than their host homologs to enhance PPP in the host during the infection [63]. The PPP gene _zwf_, encoding glucose-6-phosphate dehydrogenase (G6 PDH), catalyzes the conversion of glucose-6-phosphate to ribulose 5-phosphate and produces NADPH and CO\({}_{2}\). The 6-phosphogluconate dehydrogenase, encoded by _gnd_, catalyzes the conversion of gluconate 6-phosphate to gluconolactone 6-phosphate and produces NADPH. Currently, there are only two known enzymes shown to produce NADPH in the PPP. However, until now, little research has been done to explore the cyanophage _zwf_ and _gnd_ genes. This study shows that _zwf_ and _gnd_ are present in 25/153 and 22/153, respectively, of the sequenced cyanophage genomes. The expression of the phage _talC_, _gnd_, and _zwf_ genes may augment the PPP and produce more NADPH and the R5P that phages need for dNTP biosynthesis [63]. It is likely that after infection more NADPH would be directed toward phage DNA synthesis through the expression of these four phage genes. In the same study, researchers also found that after infection, the host NADPH/NADP ratio increased twofold, which was consistent with the inhibition of the Calvin cycle and the enhancement of PPP [63]. In a recent study [85], about 4 h infection with phage S-PM2 resulted in the cessation of CO\({}_{2}\) fixation in _Synchococcus_ sp. WH7803. For phage S-RSM4, after about 2 h infection, the CO\({}_{2}\) fixation in WH7803 was stopped. This is consistent with our analysis. In addition, with the phage genes _cp12 gnd_, _zwf_, and _talc_, S-RSM4 can suspend the CO\({}_{2}\) fixation of the host faster than phage S-PM2 without these genes.