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Nat Chem Biol. 2010 Jan;6(1):9-18. doi: 10.1038/nchembio.286.

Follow the leader: the use of leader peptides to guide natural product biosynthesis.

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Department of Chemistry, Howard Hughes Medical Institute, and Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.


The avalanche of genomic information in the past decade has revealed that natural product biosynthesis using the ribosomal machinery is much more widespread than originally anticipated. Nearly all of these compounds are crafted through post-translational modifications of a larger precursor peptide that often contains the marching orders for the biosynthetic enzymes. We review here the available information for how the peptide sequences in the precursors govern the post-translational tailoring processes for several classes of natural products. In addition, we highlight the great potential these leader peptide-directed biosynthetic systems offer for engineering conformationally restrained and pharmacophore-rich products with structural diversity that greatly expands the proteinogenic repertoire.

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