It should be noted that a 34 residue code exists based on an 8 Å distance around the A domain active site, measured by Rausch et al., but no residue positions were reported for comparison to existing bacterial codes. The 15AA code reported by Khurana and co-workers was determined by measuring a 6 Å distance around a docked substrate in homology models of members of the acyl:CoA synthetase superfamily. Several computational and directed evolution experiments have also confirmed the importance of some residue positions, specifically sites 278 and 301 (either one or both). A phylogenetic study of all classes of fungal adenylating enzymes recently confirmed the importance of the first positions of the code, namely residues 234, 235, 236, and 239, but noted that the fungal A domain code diverges significantly from well-studied bacterial examples. The question of a fungal A domain selectivity code has been addressed by several groups as described here, and we have contributed an 18AA code for fungal A domains and activation of noncanonical building blocks. In brief, homology models generated by AlphaFold were used to determine all residues within a radius of 5 Å of the active site, and this putative code was then biochemically verified by mutagenesis of a characterized fungal A domain. It appears that structural data is indeed a superior predictor of substrate preference than primary sequence alignments alone.