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Commun Biol. 2019 Feb 28;2:83. doi: 10.1038/s42003-019-0333-6. eCollection 2019.

Computational identification of co-evolving multi-gene modules in microbial biosynthetic gene clusters.

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1Manchester Centre for Synthetic Biology of Fine and Speciality Chemicals (SYNBIOCHEM), Manchester Institute of Biotechnology, Faculty of Science and Engineering, University of Manchester, 131 Princess Street, Manchester, M1 7DN United Kingdom.
2Structural & Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany.
3Bioinformatics Group, Wageningen University, Droevendaalsesteeg 1, 6708PB Wageningen, The Netherlands.


The biosynthetic machinery responsible for the production of bacterial specialised metabolites is encoded by physically clustered group of genes called biosynthetic gene clusters (BGCs). The experimental characterisation of numerous BGCs has led to the elucidation of subclusters of genes within BGCs, jointly responsible for the same biosynthetic function in different genetic contexts. We developed an unsupervised statistical method able to successfully detect a large number of modules (putative functional subclusters) within an extensive set of predicted BGCs in a systematic and automated manner. Multiple already known subclusters were confirmed by our method, proving its efficiency and sensitivity. In addition, the resulting large collection of newly defined modules provides new insights into the prevalence and putative biosynthetic role of these modular genetic entities. The automated and unbiased identification of hundreds of co-evolving group of genes is an essential breakthrough for the discovery and biosynthetic engineering of high-value compounds.

Conflict of interest statement

The authors declare no competing interests.

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