Beyond α-hydroxy acid activation, some NRPS pathways, including depsipeptide synthetases, incorporate α-keto acid building blocks. There is only one example of a crystallized α-keto acid A domain, which is the α-ketoisocaproic acid (α-Kic) selecting StsA_A from cereulide biosynthesis. This A domain structure was obtained as part of a larger study on depsipeptide synthetase modules, but there were some striking substrate interactions that were reported. Similar to previous reports on α-keto acid A domains, the α-amino contacting aspartate residue in StsA_A has been replaced with a the hydrophobic residue I306 (StsA_A numbering). This is also similar to the α-hydroxy acid A domains discussed above that maintain either an alanine or glycine in this position. From this structure, the only other molecular contact that was deemed essential for α-keto acid binding was the backbone carbonyl between G414 and M415 (Figure ).