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On the Risks of Phylogeny-Based Strain Prioritization for Drug Discovery: Streptomyces lunaelactis as a Case Study

Authors :
Loïc Martinet
Aymeric Naômé
Dominique Baiwir
Edwin De Pauw
Gabriel Mazzucchelli
Sébastien Rigali
Source :
Biomolecules, Vol 10, Iss 7, p 1027 (2020)
Publication Year :
2020
Publisher :
MDPI AG, 2020.

Abstract

Strain prioritization for drug discovery aims at excluding redundant strains of a collection in order to limit the repetitive identification of the same molecules. In this work, we wanted to estimate what can be unexploited in terms of the amount, diversity, and novelty of compounds if the search is focused on only one single representative strain of a species, taking Streptomyces lunaelactis as a model. For this purpose, we selected 18 S. lunaelactis strains taxonomically clustered with the archetype strain S. lunaelactis MM109T. Genome mining of all S. lunaelactis isolated from the same cave revealed that 54% of the 42 biosynthetic gene clusters (BGCs) are strain specific, and five BGCs are not present in the reference strain MM109T. In addition, even when a BGC is conserved in all strains such as the bag/fev cluster involved in bagremycin and ferroverdin production, the compounds produced highly differ between the strains and previously unreported compounds are not produced by the archetype MM109T. Moreover, metabolomic pattern analysis uncovered important profile heterogeneity, confirming that identical BGC predisposition between two strains does not automatically imply chemical uniformity. In conclusion, trying to avoid strain redundancy based on phylogeny and genome mining information alone can compromise the discovery of new natural products and might prevent the exploitation of the best naturally engineered producers of specific molecules.

Details

Language :
English
ISSN :
2218273X and 98764179
Volume :
10
Issue :
7
Database :
Directory of Open Access Journals
Journal :
Biomolecules
Publication Type :
Academic Journal
Accession number :
edsdoj.5af9876417944428a3cb8f8c16ecfed9
Document Type :
article
Full Text :
https://doi.org/10.3390/biom10071027