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Genome neighborhood network reveals insights into enediyne biosynthesis and facilitates prediction and prioritization for discovery

  • Jeffrey D. Rudolf
  • Xiaohui Yan
  • Ben Shen
Natural Products

Abstract

The enediynes are one of the most fascinating families of bacterial natural products given their unprecedented molecular architecture and extraordinary cytotoxicity. Enediynes are rare with only 11 structurally characterized members and four additional members isolated in their cycloaromatized form. Recent advances in DNA sequencing have resulted in an explosion of microbial genomes. A virtual survey of the GenBank and JGI genome databases revealed 87 enediyne biosynthetic gene clusters from 78 bacteria strains, implying that enediynes are more common than previously thought. Here we report the construction and analysis of an enediyne genome neighborhood network (GNN) as a high-throughput approach to analyze secondary metabolite gene clusters. Analysis of the enediyne GNN facilitated rapid gene cluster annotation, revealed genetic trends in enediyne biosynthetic gene clusters resulting in a simple prediction scheme to determine 9- versus 10-membered enediyne gene clusters, and supported a genomic-based strain prioritization method for enediyne discovery.

Keywords

Enediyne polyketide synthase Genome neighborhood network Biosynthetic gene cluster Genome mining Natural products 

Notes

Acknowledgments

This work is supported in part by the National Institutes of Health Grant CA78747 and the Natural Products Library Initiative at the Scripps Research Institute.

Supplementary material

10295_2015_1671_MOESM1_ESM.pdf (6.3 mb)
Supplementary material 1 (PDF 6494 kb)

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Copyright information

© Society for Industrial Microbiology and Biotechnology 2015

Authors and Affiliations

  1. 1.Department of ChemistryThe Scripps Research InstituteJupiterUSA
  2. 2.Department of Molecular TherapeuticsThe Scripps Research InstituteJupiterUSA
  3. 3.Natural Products Library InitiativeThe Scripps Research InstituteJupiterUSA

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