Posttranslational modification of
amino acids confers a range of structural features and activities on ribosomally synthesized
peptides, many of which have potent antimicrobial or other
biological activities.
Cypemycin is an extensively modified linear
peptide produced by Streptomyces sp. OH-4156 with potent in vitro activity against mouse
leukemia cells.
Cypemycin does not contain
lanthionine bridges but exhibits some of the structural features of
lantibiotics, notably dehydrated threonines (dehydrobutyrines) and a C-terminal S-[(Z)-2-aminovinyl]-D-
cysteine. Consequently it was classified as a member of the
lantibiotic family of posttranslationally modified
peptides.
Cypemycin also possesses two L-allo-
isoleucine residues and an N-terminal
N,N-dimethylalanine, both unique
amino acid modifications. We identified and heterologously expressed the
cypemycin biosynthetic gene cluster and performed a mutational analysis of each individual gene. We show that even the previously described modifications are carried out by unusual
enzymes or via a modification pathway unrelated to
lantibiotic biosynthesis. Bioinformatic analysis revealed the widespread occurrence of
cypemycin-like gene clusters within the bacterial kingdom and in the Archaea.
Cypemycin is the founding member of an unusual class of posttranslationally modified ribosomally synthesized
peptides, the linaridins.