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

Nature Chemical Biology volume 6, pages 9–18 (2010)Cite this article

Abstract

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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Figure 1: General scheme and examples of leader peptide–directed biosynthesis.
Figure 2: Post-translational modifications in lantibiotics.
Figure 3: Post-translational modifications in microcin and cytolysin biosynthesis.
Figure 4: Proposed biosynthesis of patellamides C and A.
Figure 5: Biosynthesis of thiostrepton.
Figure 6: Post-translational modifications in conopeptides.

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Acknowledgements

Our work on LDB has been supported by the US National Institutes of Health (GM58822). We thank D. Mitchell (University of Illinois at Urbana-Champaign) for helpful discussions.

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

    Trent J Oman & Wilfred A van der Donk

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  1. Trent J Oman
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  2. Wilfred A van der Donk
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Correspondence to Wilfred A van der Donk.

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Oman, T., van der Donk, W. Follow the leader: the use of leader peptides to guide natural product biosynthesis. Nat Chem Biol 6, 9–18 (2010). https://doi.org/10.1038/nchembio.286

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