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.

Clostrindolin is an antimycobacterial pyrone alkaloid from Clostridium beijerinckii.

Anaerobic bacteria represent an underexplored source of bioactive natural products with unusual structural features. Here we report the isolation and structure elucidation of an antimycobacterial natural product, clostroindolin, produced by Clostridium beijerinckii. Furthermore, we provide first insights into structure activity relationships, which might guide the development of novel antibiotics against mycobacteria.