<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>Cyclic nucleotides are well-known second messengers involved in the regulation of
important metabolic pathways or virulence factors. There are six different classes
of nucleotide cyclases that can accomplish the task of generating cAMP, and four
of these are restricted to the prokaryotes. The role of cAMP has been implicated in
the virulence and regulation of secondary metabolites in the phylum Actinobacteria, which contains 
important pathogens, such as <italic>Mycobacterium tuberculosis, M. leprae, M. bovis</italic> 
and <italic>Corynebacterium</italic>, and industrial organisms from the genus <italic>Streptomyces</italic>.
We have analysed the actinobacterial genome sequences found in current databases
for the presence of different classes of nucleotide cyclases, and find that only class
III cyclases are present in these organisms. Importantly, prominent members such as
<italic>M. tuberculosis</italic> and <italic>M. leprae</italic> have 17 and 4 class III cyclases, respectively, encoded
in their genomes, some of which display interesting domain fusions seen for the
first time. In addition, a pseudogene corresponding to a cyclase from <italic>M. avium</italic> has
been identified as the only cyclase pseudogene in <italic>M. tuberculosis</italic> and <italic>M. bovis</italic>. The
<italic>Corynebacterium</italic> and <italic>Streptomyces</italic> genomes encode only a single adenylyl cyclase
each, both of which have corresponding orthologues in <italic>M. tuberculosis</italic>. A clustering
of the cyclase domains in Actinobacteria reveals the presence of typical eukaryote-like,
fungi-like and other bacteria-like class III cyclase sequences within this phylum,
suggesting that these proteins may have significant roles to play in this important
group of organisms.</p>
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Comp Funct Genomics. 2004 Feb; 5(1):17-38