Open AccessA comparative metabologenomic approach reveals mechanistic insights into Streptomyces antibiotic crypticity
Author(s) -
Yunci Qi,
Keshav Kumar Nepal,
Joshua A. V. Blodgett
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2103515118
Subject(s) - streptomyces griseus , biology , gene , computational biology , streptomyces , genome , genetics , clade , indel , drug discovery , bioinformatics , bacteria , phylogenetics , genotype , single nucleotide polymorphism
Significance Streptomyces genomes harbor a trove of biosynthetic gene clusters (BGCs) that encode for drug-like molecules. However, only a fraction of these readily yield expected products. To investigate why this is, we used polycyclic tetramate macrolactam (PTM) antibiotic production as a model system. By comparing the genomes and PTM production profiles of several closely relatedStreptomyces griseus clade members, we uncovered two mechanisms that differentiate more robust producers from weaker ones. The first involves small insertion–deletion lesions in PTM BGC promoters that significantly modulate production. The second mechanism involves biosynthetic pathway interactions, in which robust PTM producers unexpectedly benefit from griseorhodin coproduction, and weaker producers lack the pathway. We highlight comparative metabologenomics as a powerful approach to understand antibiotic crypticity.