title: Genome neighborhood network reveals insights into enediyne biosynthesis and facilitates prediction and prioritization for discovery.
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.
authors: Department of Chemistry, The Scripps Research Institute, Jupiter, FL, 33458, USA.
authors: Jeffrey D
authors: JD
authors: Rudolf
authors: Department of Chemistry, The Scripps Research Institute, Jupiter, FL, 33458, USA.
authors: Xiaohui
authors: X
authors: Yan
authors: Department of Chemistry, The Scripps Research Institute, Jupiter, FL, 33458, USA. shenb@scripps.edu.|Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL, 33458, USA. shenb@scripps.edu.|Natural Products Library Initiative, The Scripps Research Institute, Jupiter, FL, 33458, USA. shenb@scripps.edu.
authors: Ben
authors: B
authors: Shen
mesh_terms: D001419:Bacteria / Q000201:enzymology / Q000235:genetics; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism; D053898:Biosynthetic Pathways / Q000235:genetics*; D055808:Drug Discovery; D053281:Enediynes / Q000737:chemistry / Q000378:metabolism*; D016680:Genome, Bacterial / Q000235:genetics*; D023281:Genomics; D058977:Molecular Sequence Annotation; D005810:Multigene Family / Q000235:genetics; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism; D064210:Secondary Metabolism / Q000235:genetics
chemical_list: D001688:Biological Products; D053281:Enediynes; D048630:Polyketide Synthases
keywords: Biosynthetic gene cluster; Enediyne polyketide synthase; Genome mining; Genome neighborhood network; Natural products