Discovery of phosphonic acid natural products by mining the genomes of 10,000 actinomycetes

Proceedings of the National Academy of Sciences of the United States of America
Kou-San JuWilliam W Metcalf

Abstract

Although natural products have been a particularly rich source of human medicines, activity-based screening results in a very high rate of rediscovery of known molecules. Based on the large number of natural product biosynthetic genes in microbial genomes, many have proposed "genome mining" as an alternative approach for discovery efforts; however, this idea has yet to be performed experimentally on a large scale. Here, we demonstrate the feasibility of large-scale, high-throughput genome mining by screening a collection of over 10,000 actinomycetes for the genetic potential to make phosphonic acids, a class of natural products with diverse and useful bioactivities. Genome sequencing identified a diverse collection of phosphonate biosynthetic gene clusters within 278 strains. These clusters were classified into 64 distinct groups, of which 55 are likely to direct the synthesis of unknown compounds. Characterization of strains within five of these groups resulted in the discovery of a new archetypical pathway for phosphonate biosynthesis, the first (to our knowledge) dedicated pathway for H-phosphinates, and 11 previously undescribed phosphonic acid natural products. Among these compounds are argolaphos, a broad-spectrum antibac...Continue Reading

References

Oct 1, 1982·Antimicrobial Agents and Chemotherapy·F R AthertonD Westmacott
Jan 1, 1980·The Journal of Antibiotics·M OkuharaH Imanaka
Feb 25, 2005·Nature Reviews. Drug Discovery·Frank E Koehn, Guy T Carter
Oct 27, 2005·Angewandte Chemie·Helge B Bode, Rolf Müller
May 4, 2006·Annual Review of Plant Biology·Barbara Ann Halkier, Jonathan Gershenzon
Jul 17, 2007·Nature Chemical Biology·Joshua A V BlodgettWilliam W Metcalf
Apr 9, 2008·Journal of Medicinal Chemistry·Gregory L Challis
Jun 6, 2009·Annual Review of Biochemistry·William W Metcalf, Wilfred A van der Donk
Feb 10, 2010·Chemistry & Biology·Svetlana A BorisovaWilliam W Metcalf
Mar 10, 2010·BMC Bioinformatics·Doug HyattLoren J Hauser
Nov 13, 2010·Current Opinion in Chemical Biology·Ry R Forseth, Frank C Schroeder
Nov 16, 2010·Future Microbiology·Heike Brötz-Oesterhelt, Peter Sass
May 4, 2011·Antimicrobial Agents and Chemotherapy·Benjamin T CircelloWilliam W Metcalf
Apr 19, 2012·The Journal of Antibiotics·János Bérdy
Jan 11, 2013·Proceedings of the National Academy of Sciences of the United States of America·Fang-Yuan Chang, Sean F Brady
Feb 23, 2013·Biochimica Et Biophysica Acta·Gordon M Cragg, David J Newman
Jun 19, 2013·Proceedings of the National Academy of Sciences of the United States of America·Despina J BougioukouWilfred A van der Donk
Jul 5, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jeremy G OwenSean F Brady
Nov 26, 2013·Journal of Industrial Microbiology & Biotechnology·Kou-San JuWilliam W Metcalf
Dec 4, 2013·Proceedings of the National Academy of Sciences of the United States of America·Xiaomin YuWilliam W Metcalf
Dec 18, 2013·Journal of Industrial Microbiology & Biotechnology·Brian O BachmannRichard H Baltz
Jan 21, 2014·Journal of Natural Products·Joel P CioniWilliam W Metcalf
Mar 7, 2014·Microbiology and Molecular Biology Reviews : MMBR·Bjarne Hove-JensenBjarne Jochimsen
Sep 27, 2014·Current Opinion in Biotechnology·Yunzi LuoHuimin Zhao
Sep 30, 2014·Nature Chemical Biology·James R DoroghaziWilliam W Metcalf
Jun 19, 2015·Biotechnology Advances·Usama Ramadan AbdelmohsenUte Hentschel

❮ Previous
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Citations

Jan 8, 2016·Journal of Industrial Microbiology & Biotechnology·Leonard Katz, Richard H Baltz
Feb 3, 2016·Current Opinion in Chemical Biology·Jason P ChinJohn P Quinn
Apr 27, 2016·Current Opinion in Biotechnology·Andrew C PawlowskiGerard D Wright
Oct 19, 2016·Current Opinion in Microbiology·Mark S ButlerMatthew A Cooper
Sep 7, 2016·Frontiers in Microbiology·Polpass Arul Jose, Bhavanath Jha
Jan 7, 2017·Chemical Reviews·Mireille MoutiezMuriel Gondry
Jan 20, 2017·ACS Synthetic Biology·Todd S FreestoneHuimin Zhao
Oct 28, 2016·Chemical Reviews·Geoff P Horsman, David L Zechel
Dec 9, 2017·Science·David A BornCatherine L Drennan
Mar 16, 2018·The Journal of Biological Chemistry·Michelle N GoettgeWilliam W Metcalf
Jul 14, 2017·Chemistry : a European Journal·Katharina PallitschChristian Stieger
Aug 19, 2017·Natural Product Reports·Olga Genilloud
Dec 19, 2017·Virus Evolution·Migun ShakyaOlga Zhaxybayeva
Sep 11, 2018·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·M Cemre ManavDitlev E Brodersen
May 4, 2016·Journal of Bacteriology·Tomas Gverzdys, Justin R Nodwell
Jan 25, 2019·Drug Discoveries & Therapeutics·Zhongyue LiYuemao Shen
Jun 22, 2019·International Journal of Systematic and Evolutionary Microbiology·Hisayuki Komaki, Tomohiko Tamura
Nov 9, 2017·Beilstein Journal of Organic Chemistry·Charlotte M SevrainPaul-Alain Jaffrès
May 12, 2020·Microbial Genomics·Arwyn EdwardsSara M E Rassner
Aug 20, 2019·Nature Communications·Kyle RiceGeoff P Horsman
Aug 28, 2019·Nature Chemical Biology·Elizabeth I ParkinsonWilliam W Metcalf
Feb 12, 2017·Journal of Industrial Microbiology & Biotechnology·Arpan A BandyopadhyayWei-Shou Hu
Feb 2, 2017·Frontiers in Microbiology·Scott W BehieMatthew F Traxler
May 4, 2017·Proceedings of the National Academy of Sciences of the United States of America·Cameron R PyeRoger G Linington
Dec 13, 2017·Proceedings of the National Academy of Sciences of the United States of America·Guohui PanBen Shen
Feb 8, 2020·Scientific Reports·Kaitlyn C BelknapCheryl P Andam
Jun 18, 2016·Archiv der Pharmazie·Katja M Fisch, Till F Schäberle
Apr 8, 2018·Biochemical Society Transactions·Lin WangCostas D Maranas

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