Some A domains activate unique building blocks, and one such pathway is the fungal siderophore SidN, which generates ferrichromes. Specifically, the third A domain of SidN activates and incorporates N δ -cis-anhydromevalonyl-N δ -hydroxy-L-ornithine (cis-AMHO). Of note, SidN_A3 is the only fungal adenylation domain that has been crystallized to date. The structure of cis-AMHO is large and quite unusual compared to other NRPS building blocks (Figure ), and the authors noted that of the 17 identified binding pocket residues in SidN_A3, five were glycine. This was thought to aid in the accommodation of such a large substrate. As the pocket of SidN_A3 is so specific, made up of F198, W202, I206, F222, D231, V232, G235, E236, L239, G272, Y293, G295, V296, G297, V320, I328 and G329 (GrsA_A numbering), it was found to exclusively activate cis-AMHO (Figure ). This new 17 amino acid "code" (17AA code B, Table ) for fungal siderophore synthetases also shared a few residues with previously identified expanded codes. It should be noted that because SidN_A3 was crystallized without a substrate, it was in the "open" conformation, and the essential C-terminal lysine residue (K517, GrsA_A numbering) was shifted ~11 Å away from the binding pocket and not observed to interact with cis-AMHO upon docking analysis. ObiF1 is a unique NRPS module that activates (2S,3R)-β-hydroxy-p-nitrohomophenylalanine (hnhF) in obafluorin biosynthesis. Similar to Thr1, the substrate β-hydroxy is coordinated by main chain atoms instead of residue side chains, namely G736, G737 and G764 (ObiF1 numbering) (Figure ). The orientation of G764 specifically may be influenced by I765, conserved in Thr1, to allow for a hydrogen bond to form between the G764 carbonyl and the βhydroxyl group of hnhF. The partial substrate selectivity code of ObiF1 is DAWGCGMI, which is similar to GrsA_A (DAWTIAAICK), but the differences provide a hydrophobic pocket for the p-nitro-phenyl group to avoid the otherwise polar, charged contacts along the peptide backbone.