Science, published online 16 December 2011, doi:10.1126/science.1210858

The tricarboxylic acid (TCA) cycle, one of the fundamental biochemical processes in metabolism, generates energy by converting acetate into CO2, H2O and important metabolic precursors. Surprisingly, cyanobacteria do not have a copy of 2-oxoglutarate dehydrogenase (2-OGDH), one of the traditional TCA enzymes, spurring alternate theories about how these species meet their metabolic needs. Mycobacterium spp. are known to use 2-oxoglutarate decarboxylase (2-OGDC) in tandem with succinic semialdehyde dehydrogenase (SSADH) as an alternative to 2-OGDH, but cyanobacteria also lack any obvious homologs of 2-OGDC. However, cyanobacteria do encode an SSADH homolog, suggesting to Zhang and Bryant that an unrecognized version of the decarboxylase might also exist. Gene neighborhood analysis of Synechococcus sp. PCC 7002 identified a two-gene operon encoding SSADH and a second putative enzyme with the same cofactor dependence as the other 2-oxoglutarate–converting enzymes. Analysis of purified proteins showed that the putative 2-OGDC produced an aldehyde, as expected, and a coupled assay confirmed the conversion of 2-oxoglutarate to succinate. Cellular assays indicated that the enzymes were present, functional and required for normal growth. Bioinformatics identified the new gene in numerous species, suggesting that this alternate solution is widely adopted. Though it remains to be seen how the two 2-OGDC enzymes are divergent in sequence yet overlapping in function, this result should initiate a substantial rethinking of cyanobacterial metabolism.