Facile
Removal of Leader Peptides from Lanthipeptides by Incorporation of
a Hydroxy Acid
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Abstract
The biosynthesis of ribosomally synthesized
and post-translationally modified peptide (RiPP) natural products
typically involves a precursor peptide which contains a leader peptide
that is important for the modification process, and that is removed
in the final step by a protease. Genome mining efforts for new RiPPs
are often hampered by the lack of a general method to remove the leader
peptides. We describe here the incorporation of hydroxy acids into
the precursor peptides in <i>E. coli</i> which results in
connection of the leader peptide via an ester linkage that is readily
cleaved by simple hydrolysis. We demonstrate the method for two lantibiotics,
lacticin 481 and nukacin ISK-1