Incorporating non-canonical amino acids (AAs) can expand AMP diversity beyond the "AMP-similarity basin" resulting from many ML models. de-novo designed AMPs using a Maximum of Auto-and Cross-Covariances (MACC) algorithm, reporting two peptides with broad-spectrum activity. The same algorithm was also used to optimize a non-active starting structure into an active AMP using an extended amino acid alphabet of 87 residues. Non-canonical residues like those found in lugdunin (thiazolidine) or exemplify how structural novelty may enhance AMP activity.