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

Journal of Industrial Microbiology & Biotechnology
Jeffrey D RudolfBen Shen

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.

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Citations

Jan 8, 2016·Journal of Industrial Microbiology & Biotechnology·Leonard Katz, Richard H Baltz
Oct 13, 2016·The Journal of Antibiotics·Zhikai GuoBen Shen
Oct 28, 2016·Chemical Reviews·Geoff P Horsman, David L Zechel
Jun 9, 2016·Natural Product Reports·Nadine ZiemertTilmann Weber
May 4, 2016·Journal of Bacteriology·Tomas Gverzdys, Justin R Nodwell
Jan 25, 2019·Drug Discoveries & Therapeutics·Zhongyue LiYuemao Shen
Jun 25, 2016·Beilstein Journal of Organic Chemistry·Juliane KorpMarkus Nett
Dec 13, 2017·Proceedings of the National Academy of Sciences of the United States of America·Guohui PanBen Shen
Nov 30, 2018·Journal of Industrial Microbiology & Biotechnology·Dandan ChenWen Liu
Jun 5, 2019·Chemical Science·Jing ShiHui Ming Ge
Nov 15, 2018·Journal of Industrial Microbiology & Biotechnology·Christiana N TeijaroBen Shen
May 23, 2019·Frontiers in Genetics·Joseph D Romano, Nicholas P Tatonetti
Oct 2, 2019·The Journal of Biological Chemistry·Andrew D SteeleBen Shen
Mar 18, 2021·PloS One·Apiwat SangphukieoMarasri Ruengjitchatchawalya
Jun 26, 2018·Cell Chemical Biology·Chin-Yuan ChangBen Shen
Jun 25, 2021·Nature Communications·Kirstin Scherlach, Christian Hertweck
Jul 24, 2021·Journal of the American Chemical Society·Guang-Lei MaZhao-Xun Liang
Aug 16, 2018·Journal of Natural Products·Jana BraeselAlessandra S Eustáquio
Aug 24, 2021·AMB Express·Hailey E Beal, Nicole A Horenstein
Nov 5, 2021·Natural Product Reports·Katherine D BaumanJonathan R Chekan

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