Linking biosynthetic and chemical space to accelerate microbial secondary metabolite discovery

Soldatou, S., Hjorleifsson Eldjarn, G., Huerta Uribe, A., Rogers, S. and Duncan, K. R. (2019) Linking biosynthetic and chemical space to accelerate microbial secondary metabolite discovery. FEMS Microbiology Letters, (doi:10.1093/femsle/fnz142) (Early Online Publication)

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Abstract

Abstract Secondary metabolites can be viewed as a chemical language, facilitating communication between microorganisms. From an ecological point of view, this metabolite exchange is in constant flux due to evolutionary and environmental pressures. From a biomedical perspective, the chemistry is unsurpassed for its antibiotic properties. Genome sequencing of microorganisms has revealed a large reservoir of Biosynthetic Gene Clusters (BGCs), however, linking these to the secondary metabolites they encode is currently a major bottleneck to chemical discovery. This linking of genes to metabolites with experimental validation will aid the elicitation of silent or cryptic (not expressed under normal laboratory conditions) BGCs. This will accelerate chemical dereplication, our understanding of gene transcription and provide a more comprehensive resource for synthetic biology. This will ultimately result in an improved understanding of both the biosynthetic and chemical space. In recent years, integrating these complex metabolomic and genomic data sets has been achieved using a spectrum of manual and automated approaches. In this review, we cover examples of these approaches, while addressing current challenges and future directions in linking these datasets.

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rogers, Dr Simon and Hjorleifsson Eldjarn, Mr Grimur and Huerta Uribe, Alejandro
Authors: Soldatou, S., Hjorleifsson Eldjarn, G., Huerta Uribe, A., Rogers, S., and Duncan, K. R.
College/School:College of Medical Veterinary and Life Sciences
College of Science and Engineering > School of Computing Science
Journal Name:FEMS Microbiology Letters
Publisher:Oxford University Press
ISSN:0378-1097
ISSN (Online):1574-6968
Copyright Holders:Copyright © 2019 FEMS
First Published:First published in FEMS Microbiology Letters 2019
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
3026970Combatting antimicrobial resistance through new software for natural product discoverySimon RogersBiotechnology and Biological Sciences Research Council (BBSRC)BB/R022054/1Computing Science