Minimum Information about a Biosynthetic Gene cluster

Medema, Marnix H.; Kottmann, Renzo; Yilmaz, Pelin; Cummings, Matthew; Biggins, John B.; Blin, Kai; Bruijn, Irene de; Chooi, Yit‐Heng; Claesen, Jan; Coates, Roger; Cruz-Morales, Pablo; Duddela, Srikanth; Düsterhus, Stephanie; Edwards, Daniel; Fewer, David P.; Garg, Neha; Geiger, Christoph; Gomez-Escribano, Juan Pablo; Greule, Anja; Hadjithomas, Michalis; Haines, Anthony S.; Helfrich, Eric J. N.; Hillwig, Matthew L.; Ishida, Keishi; Jones, Adam C.; Jones, Carla S.; Jungmann, Katrin; Kegler, Carsten; Kim, Hyun Uk; Kötter, Peter; Krug, Daniel; Masschelein, Joleen; Melnik, Alexey V.; Mantovani, Simone M.; Monroe, Emily A.; Moore, Marcus A.; Moss, Nathan A.; Nützmann, Hans-Wilhelm; Pan, Guohui; Pati, Amrita; Petras, Daniel; Reen, F. Jerry; Rosconi, Federico; Rui, Zhe; Tian, Zhenhua; Tobias, Nicholas J.; Tsunematsu, Yuta; Wiemann, Philipp; Wyckoff, Elizabeth E.; Yan, Xiaohui; Yim, Grace; Yu, Fei; Xie, Yunchang; Aigle, Bertrand; Apel, Alexander Kristian; Balibar, Carl J.; Balskus, Emily P.; Barona‐Gómez, Francisco; Bechthold, Andreas; Bode, Helge B.; Borriss, Rainer; Brady, Sean F.; Brakhage, Axel A.; Caffrey, Patrick; C, Yi; Clardy, Jon; Cox, Russell J.; Mot, René De; Donadio, Stefano; Donia, Mohamed S.; Donk, Wilfred A. van der; Dorrestein, Pieter C.; Doyle, Seán; Driessen, Arnold J. M.; Ehling‐Schulz, Monika; Entian, Karl Dieter; Fischbach, Michael A.; Gerwick, Lena; Gerwick, William H.; Gross, Harald; Gust, Bertolt; Hertweck, Christian; Höfte, Monica; Jensen, Susan E.; Ju, Jianhua; Katz, Leonard; Kaysser, Leonard; Klassen, Jonathan L.; Keller, Nancy P.; Kormanec, Ján; Kuipers, Oscar P.; Kuzuyama, Tomohisa; Kyrpides, Nikos C.; Kwon, Hyung Jin; Lautru, Sylvie; Lavigne, Rob; Lee, Chia Y.; Bai, Linquan; Liu, Xinyu; Liu, Wen; Luzhetskyy, Andriy; Mahmud, Taifo; Mast, Yvonne; Méndez, Cármen; Metsä‐Ketelä, Mikko; Micklefield, Jason; Mitchell, Douglas A.; Moore, Bradley S.; Moreira, Leonilde M.; Müller, Rolf; Neilan, Brett A.; Nett, Markus; Nielsen, Jens; O’Gara, Fergal; Oikawa, Hideaki; Osbourn, Anne; Osburne, Marcia S.; Ostash, Bohdan; Payne, Shelley M.; Pernodet, Jean‐Luc; Petřı́ček, Miroslav; Piel, Jörn; Ploux, Olivier; Raaijmakers, Jos M.; Salas, José A.; Schmitt, E.; Scott, Barry; Seipke, Ryan F.; Shen, Ben; Sherman, David H.; Sivonen, Kaarina; Smanski, Michael J.; Sosio, Margherita; Stegmann, Evi; Süssmuth, Roderich D.; Tahlan, Kapil; Thomas, Christopher M.; Tang, Yi; Truman, Andrew W.; Viaud, Muriel; Walton, Jonathan D.; Walsh, Christopher T.; Weber, Tilmann; Wezel, Gilles P. van; Wilkinson, Barrie; Willey, Joanne M.; Wohlleben, Wolfgang; Wright, Gerard D.; Ziemert, Nadine; Zhang, Changsheng; Zotchev, Sergey B.; Breitling, Rainer; Takano, Eriko; Glöckner, Frank Oliver

doi:10.1038/nchembio.1890

Cited by 735 publications

(665 citation statements)

References 30 publications

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“…This information can be used to either guide a more targeted drug discovery technique (such as reactivity‐guided isolation; Castro‐Falcón et al ., 2016) or peptide and glycogenomic approaches (Kersten et al ., 2011, 2013) or allow the heterologous expression in an optimized expression host ( activation of silent gene cluster ). Furthermore, comprehensive biosynthetic gene cluster databases such as MiBIG (Minimum Information about a Biosynthetic Gene cluster) provide the possibility to easily estimate novelty in the encoded compounds (Medema et al ., 2015). …”

Section: Novel Approaches For Drug Discoverymentioning

confidence: 99%

Antibiotic drug discovery

Wohlleben

Mast

Stegmann

et al. 2016

Microbial Biotechnology

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143

113

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SummaryDue to the threat posed by the increase of highly resistant pathogenic bacteria, there is an urgent need for new antibiotics; all the more so since in the last 20 years, the approval for new antibacterial agents had decreased. The field of natural product discovery has undergone a tremendous development over the past few years. This has been the consequence of several new and revolutionizing drug discovery and development techniques, which is initiating a ‘New Age of Antibiotic Discovery’. In this review, we concentrate on the most significant discovery approaches during the last and present years and comment on the challenges facing the community in the coming years.

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Section: Novel Approaches For Drug Discoverymentioning

confidence: 99%

Antibiotic drug discovery

Wohlleben

Mast

Stegmann

et al. 2016

Microbial Biotechnology

Self Cite

143

113

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show abstract

“…New proposals for the annotation and classification of biosynthetic gene clusters will provide the foundation to examine and reconstruct their evolutionary histories with unprecedented detail (Medema et al 2015). As more gene sequences become available, phylogenies will improve accordingly; dating resistance determinants is often an accidental by-product of phylogenetic studies aimed at classifying newly discovered resistance determinants.…”

Section: The Impact Of Technology On Our Ability To Predict the Histomentioning

confidence: 99%

The Prehistory of Antibiotic Resistance

Perry

Waglechner

Wright

2016

Cold Spring Harb Perspect Med

155

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“…The authors here developed a pipeline utilizing PSI-BLAST, which iteratively refines searches based on conserved amino acids, signal peptide detection software, and BLASTClust to further sort precursor proteins. Another method utilized in A. flavus by our group involves using known eukaryotic clusters in the MIBiG database 83) as queries against sequenced strains of A. flavus. The software program multigeneblast 84) will search a genome or set of sequences using multiple sequences as the query, thus allowing for gene rearrangement and differing degrees of identity.…”

Section: -4 Cluster Prediction In the Age Of Genomicsmentioning

confidence: 99%

<i>Aspergillus flavus</i> Secondary Metabolites: More than Just Aflatoxins

et al. 2018

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Aspergillus flavus is best known for producing the family of potent carcinogenic secondary metabolites known as aflatoxins. However, this opportunistic plant and animal pathogen also produces numerous other secondary metabolites, many of which have also been shown to be toxic. While about forty of these secondary metabolites have been identified from A. flavus cultures, analysis of the genome has predicted the existence of at least 56 secondary metabolite gene clusters. Many of these gene clusters are not expressed during growth of the fungus on standard laboratory media. This presents researchers with a major challenge of devising novel strategies to manipulate the fungus and its genome so as to activate secondary metabolite gene expression and allow identification of associated cluster metabolites. In this review, we discuss the genetic, biochemical and bioinformatic methods that are being used to identify previously uncharacterized secondary metabolite gene clusters and their associated metabolites. It is important to identify as many of these compounds as possible to determine their bioactivity with respect to fungal development, survival, virulence and especially with respect to any potential synergistic toxic effects with aflatoxin.

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Minimum Information about a Biosynthetic Gene cluster

Cited by 735 publications

References 30 publications

Antibiotic drug discovery

Antibiotic drug discovery

The Prehistory of Antibiotic Resistance

<i>Aspergillus flavus</i> Secondary Metabolites: More than Just Aflatoxins

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