Lantibiotics are ribosomally synthesized and post-translationally modified peptide natural products that contain thioether crosslinks formed by lanthionine and methyllanthionine residues. They exert potent antimicrobial activity against Gram-positive bacteria. We herein report production of analogues of two lantibiotics, lacticin 481 and nisin, that contain non-proteinogenic amino acids using two different strategies involving amber stop codon suppression technology. These methods complement recent alternative approaches to incorporate non-proteinogenic amino acids into lantibiotics.
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