Nitrogen source as a modulator of the metabolic activity of Pedobacter lusitanus NL19: a transcriptomic approach.

Secondary metabolites (SMs) are compounds with relevant biological activities. Their production under laboratory conditions, especially in broth, is still challenging. An example is the pedopeptins, which are nonribosomal peptides active against some bacteria listed by the WHO for which new antibiotics are urgently needed. Their biosynthesis is inhibited by high concentrations of peptone from casein (PC) in tryptic soy broth (TSB), and we applied a RNA-seq approach to identify Pedobacter lusitanus NL19 cellular pathways modulated by this condition. Results were validated by qPCR and revealed 261 differentially expressed genes (DEGs), 46.3% of them with a predicted biological function. Specifically, high concentration of PC significantly repressed the de novo biosynthesis of biotin (- 60X) and the production of nonribosomal peptide synthetases (NRPS) of pedopeptins (about - 14X), but no effect was observed on the expression of other NRPS. Transcription of a L-Dap synthesis operon that includes a protein with a σ-like domain was also reduced (about - 7X). High concentrations of PC led to a significant overexpression of MFS and RND efflux pumps and a ferrous iron uptake system, suggesting the redirection of cell machinery to export compounds such as amino acids, sugars and metal divalent cations, alongside with a slight increase of iron import. KEY POINTS: • Higher concentrations of phosphate sources highly repress many operons • High concentrations of peptone from casein (PC) cause biotin's operon repression • High concentrations of PC downregulate the production of peptides of unknown function.