A computational framework to explore large-scale biosynthetic diversity

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Navarro-Munoz, Jorge C. ^{[1, 2]} ; Selem-Mojica, Nelly ^[3] ; Mullowney, Michael W. ^[4] ; Kautsar, Satria A. ^[1] ; Tryon, James H. ^[4] ; Parkinson, I, Elizabeth ; De Los Santos, Emmanuel L. C. ^[5] ; Yeong, Marley ^[1] ; Cruz-Morales, Pablo ^[3] ; Abubucker, Sahar ^{[6, 7]} ; Roeters, Arne ^[1] ; Lokhorst, Wouter ^[1] ; Fernandez-Guerra, Antonio ^{[8, 9, 10]} ; Cappelini, Luciana Teresa Dias ^[4] ; Goering, Anthony W. ^[4] ; Thomson, Regan J. ^[4] ; Metcalf, William W. ^{[11, 12]} ; Kelleher, Neil L. ^[4] ; Barona-Gomez, Francisco ^[3] ; Medema, Marnix H. ^[1]

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^[1] Wageningen Univ, Bioinformat Grp, Wageningen - Netherlands

^[2] Westerdijk Fungal Biodivers Inst, Fungal Nat Prod Grp, Utrecht - Netherlands

^[3] Cinvestav IPN, Unidad Genom Avanzada Langebio, Evolut Metab Divers Lab, Irapuato - Mexico

^[4] Northwestern Univ, Dept Chem, Evanston, IL 60208 - USA

^[5] Univ Warwick, Warwick Integrat Synthet Biol Ctr, Coventry, W Midlands - England

^[6] Novartis Inst BioMed Res, Cambridge, MA - USA

^[7] Sanofi, Cambridge, MA - USA

^[8] Max Planck Inst Marine Microbiol, Microbial Genom & Bioinformat, Bremen - Germany

^[9] Univ Copenhagen, Lundbeck Fdn GeoGenet Ctr, GLOBE Inst, Copenhagen - Denmark

^[10] Univ Bremen, Ctr Marine Environm Sci, Bremen - Germany

^[11] Parkinson, Elizabeth, I, Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL - USA

^[12] Parkinson, Elizabeth, I, Univ Illinois, Dept Microbiol, Urbana, IL - USA

• Tipo de documento: Artigo Científico
• Fonte: Nature Chemical Biology; v. 16, n. 1, p. 60+, JAN 2020.
• Citações Web of Science: 3

Resumo

Genome mining has become a key technology to exploit natural product diversity. Although initially performed on a single-genome basis, the process is now being scaled up to mine entire genera, strain collections and microbiomes. However, no bioinformatic framework is currently available for effectively analyzing datasets of this size and complexity. In the present study, a streamlined computational workflow is provided, consisting of two new software tools: the `biosynthetic gene similarity clustering and prospecting engine' (BiG-SCAPE), which facilitates fast and interactive sequence similarity network analysis of biosynthetic gene clusters and gene cluster families; and the `core analysis of syntenic orthologues to prioritize natural product gene clusters' (CORASON), which elucidates phylogenetic relationships within and across these families. BiG-SCAPE is validated by correlating its output to metabolomic data across 363 actinobacterial strains and the discovery potential of CORASON is demonstrated by comprehensively mapping biosynthetic diversity across a range of detoxin/rimosamide-related gene cluster families, culminating in the characterization of seven detoxin analogues. (AU)

• Processo FAPESP: 17/08038-8 - Busca de potenciais produtores de peptídeos não ribossômicos (NRPS) na compostagem da Fundação Parque Zoológico de São Paulo, utilizando iChip e Prism
• Beneficiário: Luciana Teresa Dias Cappelini
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado