Oak‐associated negativicute equipped with ancestral aromatic polyketide synthase produces antimycobacterial dendrubins

Anaerobic bacteria have only recently been recognized as a source of antibiotics; yet, the metabolic potential of Negativicutes (Gram‐negative staining Firmicutes) such as the oak‐associated Dendrosporobacter quercicolus has remained unknown. Genome mining of D. quercicolus and phylogenetic analyses revealed a gene cluster for a type II polyketide synthase (PKS) complex that belongs to the most ancestral enzyme systems of this type. Metabolic profiling, NMR analyses, and stable‐isotope labeling led to the discovery of a new family of anthraquinone‐type polyphenols, the dendrubins, which are diversified by acylation, methylation, and dimerization. Dendrubin A and B were identified as strong antibiotics against a range of clinically relevant, human‐pathogenic mycobacteria.