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Front Microbiol. 2018 Apr 6;9:657. doi: 10.3389/fmicb.2018.00657. eCollection 2018.

Expanding the Genetic Code of Lactococcus lactis and Escherichia coli to Incorporate Non-canonical Amino Acids for Production of Modified Lantibiotics.

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Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, Netherlands.
Biocatalysis Group, Department of Chemistry, Technische Universität Berlin (Berlin Institute of Technology), Berlin, Germany.
Institute of Medical Microbiology and Hygiene, Universität Regensburg, Regensburg, Germany.


The incorporation of non-canonical amino acids (ncAAs) into ribosomally synthesized and post-translationally modified peptides, e.g., nisin from the Gram-positive bacterium Lactococcus lactis, bears great potential to expand the chemical space of various antimicrobials. The ncAA Nε-Boc-L-lysine (BocK) was chosen for incorporation into nisin using the archaeal pyrrolysyl-tRNA synthetase-tRNAPyl pair to establish orthogonal translation in L. lactis for read-through of in-frame amber stop codons. In parallel, recombinant nisin production and orthogonal translation were combined in Escherichia coli cells. Both organisms synthesized bioactive nisin(BocK) variants. Screening of a nisin amber codon library revealed suitable sites for ncAA incorporation and two variants displayed high antimicrobial activity. Orthogonal translation in E. coli and L. lactis presents a promising tool to create new-to-nature nisin derivatives.


antimicrobial peptides; bacteriocin; nisin; non-canonical amino acids; orthogonal translation system; pyrrolysyl-tRNA synthetase; stop codon suppression

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