Journal ArticleDOI
The confluence of big data and evolutionary genome mining for the discovery of natural products.
Marc G. Chevrette,Athina Gavrilidou,Shrikant Mantri,Nelly Selem-Mojica,Nadine Ziemert,Francisco Barona-Gómez +5 more
TLDR
This review covers literature between 2003-2021 and highlights examples where Big Data and evolutionary analyses have been combined to provide bioinformatic resources and tools for the discovery of novel natural products and their biosynthetic enzymes.About:
This article is published in Natural Product Reports.The article was published on 2021-11-17. It has received 21 citations till now.read more
Citations
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A Systematic Computational Analysis of Biosynthetic Gene Cluster Evolution: Lessons for Engineering Biosynthesis - eScholarship
Andrej Sali,Michael A. Fischbach,Marnix H. Medema,Peter Cimermancic,Eriko Takano,MA Fischbach +5 more
TL;DR: By performing a systematic computational analysis of BGC evolution, this work derives evidence for three findings that shed light on the ways in which, despite these constraints, nature successfully invents new molecules.
Journal ArticleDOI
Compendium of specialized metabolite biosynthetic diversity encoded in bacterial genomes
Athina Gavriilidou,Satria A. Kautsar,Nestor Zaburannyi,Daniel Krug,Rolf Müller,Marnix H. Medema,Nadine Ziemert +6 more
TL;DR: The authors analyzed ~170,000 bacterial genomes and ~47,000 metagenome assembled genomes using a modified BiG-SLiCE and the new clust-o-matic algorithm.
Journal ArticleDOI
Microbiome composition modulates secondary metabolism in a multispecies bacterial community
Marc G. Chevrette,Chris S. Thomas,Amanda Hurley,Natalia Rosario-Meléndez,Krishnan P. Sankaran,Yixing Tu,Austin W. Hall,S.B. Magesh,Jo Handelsman +8 more
TL;DR: Results from this model community show that bacterial BGC expression and chemical output depend on the identity and biosynthetic capacity of coculture partners, suggesting community composition and microbiome interactions may shape the regulation of secondary metabolism in nature.
Journal ArticleDOI
Targeted Large-Scale Genome Mining and Candidate Prioritization for Natural Product Discovery
TL;DR: Genomics-based approaches for prioritizing candidate BGCs extracted from large-scale genomic data are discussed, by highlighting studies that have successfully produced compounds with high chemical novelty, novel biosynthesis pathway, and potent bioactivities.
Journal ArticleDOI
Integrated Metabolomic–Genomic Workflows Accelerate Microbial Natural Product Discovery
TL;DR: This work considers innovative approaches which have led to prioritization of strain targets and have mitigated rediscovery rates, and discusses integration of principles of comparative evolutionary studies and retrobiosynthetic predictions to better understand biosynthetic mechanistic details and link genome sequence to structure.
References
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Journal ArticleDOI
A roadmap for natural product discovery based on large-scale genomics and metabolomics
James R. Doroghazi,Jessica C. Albright,Anthony W. Goering,Kou San Ju,Robert R. Haines,Konstantin A. Tchalukov,David P. Labeda,Neil L. Kelleher,William W. Metcalf +8 more
TL;DR: Extrapolation from the 830-genome dataset reveals that Actinobacteria encode hundreds of thousands of future drug leads, while the strong correlation between phylogeny and GCFs frames a roadmap to efficiently access them.
Journal ArticleDOI
MIBiG 2.0: a repository for biosynthetic gene clusters of known function.
Satria A. Kautsar,Kai Blin,Simon Shaw,Jorge C. Navarro-Muñoz,Barbara R. Terlouw,Justin J. J. van der Hooft,Jeffrey A. van Santen,Vittorio Tracanna,Hernando G. Suarez Duran,Victòria Pascal Andreu,Nelly Selem-Mojica,Mohammad Alanjary,Serina L. Robinson,George Lund,Samuel C. Epstein,Ashley C. Sisto,Louise K. Charkoudian,Jérôme Collemare,Roger G. Linington,Tilmann Weber,Marnix H. Medema +20 more
TL;DR: MIBiG 2.0 is presented, which encompasses major updates to the schema, the data, and the online repository itself, and improves the user experience by adding new features such as query searches and a statistics page, and enabled direct link-outs to chemical structure databases.
Journal ArticleDOI
A genomic catalog of Earth’s microbiomes
Stephen Nayfach,Simon Roux,Rekha Seshadri,Daniel W. Udwary,Neha Varghese,Frederik Schulz,Dongying Wu,David Paez-Espino,I-Min Chen,Marcel Huntemann,Krishna Palaniappan,Joshua Ladau,Supratim Mukherjee,T. B. K. Reddy,Torben Nielsen,Edward Kirton,José P. Faria,Janaka N. Edirisinghe,Christopher S. Henry,Sean P. Jungbluth,Dylan Chivian,Paramvir S. Dehal,Elisha M. Wood-Charlson,Adam P. Arkin,Susannah G. Tringe,Axel Visel,Tanja Woyke,Nigel J Mouncey,Natalia Ivanova,Nikos C. Kyrpides,Emiley A. Eloe-Fadrosh +30 more
TL;DR: The utility of this collection of >10,000 metagenomes collected from diverse habitats covering all of Earth’s continents and oceans is demonstrated for understanding secondary-metabolite biosynthetic potential and for resolving thousands of new host linkages to uncultivated viruses.
Journal ArticleDOI
Natural products – a simple model to explain chemical diversity
Richard D. Firn,Clive G. Jones +1 more
TL;DR: A simple evolutionary model is presented which explains why organisms produce so many natural products, why so many have low biological activity, why enzymes involved in natural product synthesis have the properties they do and why natural product metabolism is shaped as it is.
Journal ArticleDOI
Exploiting the mosaic structure of trans-acyltransferase polyketide synthases for natural product discovery and pathway dissection.
TuAnh Nguyen,Keishi Ishida,Holger Jenke-Kodama,Elke Dittmann,Cristian Gurgui,Thomas Hochmuth,Stefan Taudien,Matthias Platzer,Christian Hertweck,Jörn Piel +9 more
TL;DR: It is shown that trans-AT PKSs evolved in a fundamentally different fashion from cis-AT systems, through horizontal recruitment and assembly of substrate-specific ketosynthase (KS) domains, and will facilitate both the discovery of novel polyketides by genome mining and the extraction of chemical information from short trans- AT PCR products, using metagenomic DNA of marine sponges.
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