Follow the leader: the use of leader peptides to guide natural product biosynthesis.
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.
Oman
Trent J
TJ
Department of Chemistry, Howard Hughes Medical Institute, and Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
van der Donk
Wilfred A
WA
D020816:Amino Acid Motifs; D001430:Bacteriocins / Q000737:chemistry; D001688:Biological Products / Q000096:biosynthesis* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D006801:Humans; D015394:Molecular Structure; D009561:Nisin / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D015202:Protein Engineering; D011498:Protein Precursors / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D012269:Ribosomal Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D012270:Ribosomes / Q000378:metabolism
D001430:Bacteriocins; D001688:Biological Products; D010455:Peptides; D011498:Protein Precursors; D012269:Ribosomal Proteins; C020411:microcin; D009561:Nisin