Carotenoid cleavage dioxygenases (CCDs) are a group of enzymes that catalyze the oxidative cleavage steps from carotenoids to various carotenoid cleavage products. Some ccd genes have been identified and encoded enzymes functionally characterized in many higher plants, but little in cyanobacteria. We performed a comparative analysis of ccd sequences and explored their distribution, classification, phylogeny, evolution, and structure among 37 cyanobacteria. Totally 61 putative ccd sequences were identified, which are abundant in Acaryochloris marina MBIC 11017, filamentous N2-fixing cyanobacteria, and unicellular cyanobacterial Cyanothece. According to phylogenetic trees of 16S rDNA and CCD, nced and ccd8 genes occur later than the divergence of ccd7, apco, and ccd1. All CCD enzymes share conserved basic structure domains constituted by a single loop formed with seven β-strands and one helix. In this paper, a general framework of sequence-function-evolution connection for the ccd has been revealed, which may provide new insight for functional investigation. 1. Introduction Cyanobacteria, also known as blue-green algae and blue-green bacteria, are among the earliest branching groups on earth, dating back 2.5–3.5 billion years, based on the fossil evidence [1]. They may be unicellular or filamentous and can be found in almost every conceivable environment, such as marine and freshwater habitats, soil, rocks, and plants [2, 3]. With the capacity of oxygenic photosynthesis similar to the process found in higher plants, cyanobacteria constitute a group of species diverse not only in ecological habitat, but also in genome size and the number of gene, indicating the significance of comparative genome research. The genome size varied from 1.6？Mb (Prochlorococcus sp. MIT9301) to 9.0？Mb (Nostoc punctiforme PCC 73102), and the number of gene ranged from 1,756 (Prochlorococcus marinus MED4) to 8,462 (Acaryochloris marina MBIC11017) [4–6]. A lot of information on the evolutionary history of cyanobacteria has strongly supported an underlying meaning of comparative genome research. Three major clades are observed in cyanobacteria phylogenetic tree (Figure 1). The unicellular cyanobacteria (Prochlorococcus and Synechococcus) from ocean form the first monophyletic group (BS: 98%). They maintain the smallest genome size and account for significant biomass and primary production of marine biosphere [7]. Two Synechococcus elongatus PCC (6301 and 7942) are found at the base of this monophyletic group. Three thermophilic cyanobacteria (Synechococcus sp. JA-2-3B′a (2-13),
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