Extended Data Table 1. Condensation Domains with a HHHxxxDG motif and an upstream predicted serine- or threonine-activating A Domain.

Condensation domains with a HHHxxxDG motif and an upstream putative serine- or threonine- activating A domain were identified through a tblastn search on the NCBI nucleotide database. An initial search was done using the A₄PCP₄C₅ tri-domain from the nocardicin gene cluster as a query resulting in 25532 hits from 7164 sequences under an E-value threshold of 1E-20. These hits were then filtered to exclude sequences with query coverages of < 75%, yielding 3834. All sequences were translated and parsed for HHHxxxDG motifs. The subsequent 37 sequences were submitted to NRPSPredictor2^32,33 to identify upstream predicted serine or threonine A domains. After removing duplicate sequences, a final set of 12 remained. From the final set of sequences, only those with high confidence predictions of upstream serine- or threonine-specific A domains were aligned with the nocardicin module 5 condensation domain. Analysis revealed that all sequences in the alignment displayed characteristic motifs predominantly observed in the ^DC_L subtype^34,35 of condensation domains despite the fact that nocardicin C₅ exhibits ^LC_L binding.