Article (Scientific journals)
On the Risks of Phylogeny-Based Strain Prioritization for Drug Discovery: Streptomyces lunaelactis as a Case Study
Martinet, Loïc; Naômé, A.; Baiwir, Dominique et al.
2020In Biomolecules, 10 (7)
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Abstract :
[en] 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.
Disciplines :
Microbiology
Author, co-author :
Martinet, Loïc ;  Université de Liège - ULiège > InBioS
Naômé, A.;  Hedera-22, Boulevard du Rectorat 27b, B-4000 Liège, Belgium
Baiwir, Dominique  ;  Université de Liège - ULiège > GIGA Platforms
De Pauw, Edwin  ;  Université de Liège - ULiège > Département de chimie (sciences) > Chimie analytique inorganique
Mazzucchelli, Gabriel  ;  Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
Rigali, Sébastien  ;  Université de Liège - ULiège > Département des sciences de la vie > Centre d'ingénierie des protéines
Language :
English
Title :
On the Risks of Phylogeny-Based Strain Prioritization for Drug Discovery: Streptomyces lunaelactis as a Case Study
Publication date :
2020
Journal title :
Biomolecules
eISSN :
2218-273X
Publisher :
NLM (Medline)
Volume :
10
Issue :
7
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 23 January 2021

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