RNA-seq Dactylosporangium vinaceum

Natural products have proven critical in modern medicine and metagenomics data suggests many remain to be uncovered. A likely important reservoir for such bioactive molecules are rare genera of bacteria that have thus far not been heavily studied. In addition, while many bacteria carry the encrypted potential to generate natural products, identifying the associated natural products is challenging when these biosynthetic gene clusters are not or poorly transcribed (dormant). Finally, as natural product synthesis bears a significant energy cost, it is likely that these molecules possess important bioactivity, that when understood can be exploited for alternative applications.In this work we investigate the biosynthetic potential of the rare actinomycete, Dactylosporangium vinaceum. This work reports a first-in-genera assembled genome of a Dactylosporangium bacteria, and reveals it carry a large potential to synthesis natural products. In addition, transcriptomic analysis by RNA-seq, show that despite the large potential, most biosynthetic gene clusters are poorly transcribed (dormant). Using a chemical library of molecules designed to modulate transcription, a compound, BDM44661, was identified that prevented the synthesis of an uncharacterised wine-red pigment by D. vinaceum, without impacting growth. Transcriptome analysis found BDM44661 to repress a specific biosynthetic gene cluster that is likely responsible for pigment formation. In combination with structural elucidation of compounds from the wine-red pigment, found them to belong to the family of rubrolones. Further investigation into the rubrolone family, in particular, pre-rubrolone, found it to inactivate environmental amino acids and ammonia (while being able to survive on nitrate), amino containing antibiotics, antimicrobial peptides and siderophores. This work shows that pre-rubrolone is the likely bioactive product of rubrolone biosynthesis, and that its bioactive function is to act as a promiscuous minesweeper of environmental amines.