Targeted Genome Mining-From Compound Discovery to Biosynthetic Pathway Elucidation.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractNatural products are an important source of novel investigational compounds in drug discovery. Especially in the field of antibiotics, Actinobacteria have been proven to be a reliable source for lead structures. The discovery of these natural products with activity- and structure-guided screenings has been impeded by the constant rediscovery of previously identified compounds. Additionally, a large discrepancy between produced natural products and biosynthetic potential in Actinobacteria, including representatives of the order Pseudonocardiales, has been revealed using genome sequencing. To turn this genomic potential into novel natural products, we used an approach including the in-silico pre-selection of unique biosynthetic gene clusters followed by their systematic heterologous expression. As a proof of concept, fifteen Saccharothrixespanaensis genomic library clones covering predicted biosynthetic gene clusters were chosen for expression in two heterologous hosts, Streptomyceslividans and Streptomycesalbus. As a result, two novel natural products, an unusual angucyclinone pentangumycin and a new type II polyketide synthase shunt product SEK90, were identified. After purification and structure elucidation, the biosynthetic pathways leading to the formation of pentangumycin and SEK90 were deduced using mutational analysis of the biosynthetic gene cluster and feeding experiments with 13C-labelled precursors.
CitationMicroorganisms. 2020 Dec 19;8(12):2034. doi: 10.3390/microorganisms8122034.
AffiliationHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
The following license files are associated with this item:
- Creative Commons
- Discovery of phosphonic acid natural products by mining the genomes of 10,000 actinomycetes.
- Authors: Ju KS, Gao J, Doroghazi JR, Wang KK, Thibodeaux CJ, Li S, Metzger E, Fudala J, Su J, Zhang JK, Lee J, Cioni JP, Evans BS, Hirota R, Labeda DP, van der Donk WA, Metcalf WW
- Issue date: 2015 Sep 29
- Functional Genome Mining for Metabolites Encoded by Large Gene Clusters through Heterologous Expression of a Whole-Genome Bacterial Artificial Chromosome Library in Streptomyces spp.
- Authors: Xu M, Wang Y, Zhao Z, Gao G, Huang SX, Kang Q, He X, Lin S, Pang X, Deng Z, Tao M
- Issue date: 2016 Oct 1
- Nonribosomal peptides in fungal cell factories: from genome mining to optimized heterologous production.
- Authors: Vassaux A, Meunier L, Vandenbol M, Baurain D, Fickers P, Jacques P, Leclère V
- Issue date: 2019 Dec
- Expanding our understanding of sequence-function relationships of type II polyketide biosynthetic gene clusters: bioinformatics-guided identification of Frankiamicin A from Frankia sp. EAN1pec.
- Authors: Ogasawara Y, Yackley BJ, Greenberg JA, Rogelj S, Melançon CE 3rd
- Issue date: 2015
- Deciphering chemical logic of fungal natural product biosynthesis through heterologous expression and genome mining.
- Authors: Chiang CY, Ohashi M, Tang Y
- Issue date: 2023 Jan 25